索马鲁肽口溶膜

Orodispersible films (ODFs), easy to administer, flexible in dosage, and free of choking and aspiration risks, have drawn widespread attention as pediatric formulations. However, it is a great challenge to endow ODFs with sustained release due to their fast disintegration. Herein, we designed a novel orodispersible film load with dual-coated sustained-release microparticles (SRMPs) for children using topiramate as a model drug. SRMPs with a particle size of 98.32 ± 0.22 µm, fabricated with a pellet core, a drug layer, and a coating layer, were prepared by two microparticle coating steps. The sustained-release orodispersible films (SRODFs) with uniform distribution of SRMPs and favorable disintegration time showed good formability, mechanical properties, and palatability. The factors affecting drug release of the SRMPs and the SRODFs were further explored. More importantly, pharmacokinetics study in human demonstrated that, although the SRODFs had a longer mean retention time, they were bioequivalence compared with the commercially available extended-release products (Qudexy® XR). A strong in vivo-in vitro correlation of the SRODFs was established. Notably, the SRODFs can be loaded with other drugs other than topiramate, offering a promising formulation option for pediatric patients with different diseases.

BACKGROUND Oral diseases affect over three billion peopleand are among the most commonly observed infections worldwide. Recent studies have shown that controlling the ecology of the oralome is more effective in reducing the risk of caries than the complete removal of both harmful and beneficial microorganisms. This work aimed to develop a strategy for preventing dysbiosis in the oral cavity by applying a postbiotic-based orodispersible film. METHODS Lactiplantibacillus plantarum 226V and Lacticaseibacillus paracasei L26 were cultured in De Man-Rogosa-Sharpe (MRS) broth for 48 hours, followed by centrifugation and filtration. Then, the resultant postbiotics were then subjected to various dilutions (10% (v/v), 20% (v/v), 40% (v/v), 60% (v/v) and 100% (v/v)) and co-incubated with Streptococcus mutans. Antimicrobial efficacy, minimal inhibitory concentration, the time required to inhibit S. mutans growth, and antibiofilm properties of the postbiotics were assessed. Subsequently, an orodispersible film comprising polymers and plasticizers, namely Xanthan gum, maltodextrin, and glycerol, was developed as a vehicle for postbiotic delivery. Formulation optimization, physical property evaluation, and cytotoxicity against the TR146 human oral cell line (TR146 cell line) were conducted. RESULTS Postbiotics demonstrated antimicrobial and antibiofilm activity against S. mutans following 24-hour co-incubation. The minimal inhibitory concentration for combined postbiotics administration was 20% (v/v). Remarkably, 79.6 ± 8.15% inhibition of biofilm formation was achieved using 100% (v/v) of the postbiotic derived from L. plantarum 226V. Incorporating postbiotics did not compromise the dissolution time of orodispersible films, all exceeding 20 minutes. Furthermore, solubility improved following postbiotic addition, facilitating ease of handling. Importantly, postbiotic-impregnated orodispersible films were non-cytotoxic when exposed to the TR146 cell line. CONCLUSIONS These findings underscore the potential of orodispersible films loaded with postbiotics as a promising potential intervention for oral dysbiosis.

Fixed-dose combination (FDC) of antihypertensive drugs improve efficacy, safety, and patient adherence over monotherapy. However, a FDC of telmisartan (TEL) and indapamide (IND), both poorly soluble BCS Class II drugs, has not been available yet. This study aimed to develop an orodispersible film (ODF) containing TEL and IND cyclodextrin (CD) inclusion complexes (ICs) to enhance solubility and offer a patient adherence dosage form. In the first phase of the study, phase-solubility analysis was performed with β-CD then the ICs were prepared via kneading and assessed for solubility enhancement and entrapment efficiency. In the second phase, ICs were incorporated into hydroxypropyl-methylcellulose (HPMC) based ODFs using solvent casting. The films were characterized for thickness, mass and content uniformity, surface pH, water content, folding endurance, Young’s modulus, FTIR, in vitro disintegration and dissolution. AL-type phase-solubility plots confirmed 1:1 complexation and enhanced solubility by 1.7–4.1 fold, with entrapment efficiency >95%. ICs-loaded ODFs were thin (0.138 mm), uniform in mass (236.39 mg) and content (TEL 97.22%, IND 102.09%), nearly neutral pH, and low in water (2.68%). Mechanical testing showed adequate flexibility and stiffness (100 N.mm⁻² modulus). Disintegration occurred in

ABSTRACT. Lamotrigine (LTG), classified as BCS class II, is dissolved in cosolvent ethanol (EtOH) or ethyl acetate (EA) to enhance solubility. The objectives of this study are to identify the appropriate formulation of LTG orodispersible film (OF) based on hydroxypropyl methylcellulose Pharmacoat® 603 and polyvinyl alcohol (HPMC P.603/PVA) polymer with EtOH or EA solvency using Central Composite Design in Response Surface Methodology (CCD-RSM). An experimental approach was utilized to investigate the effect of cosolvent amount and HPMC P.603/PVA ratios on the film disintegration time (DT) and folding endurance (FE). The optimized OF-EA composition was 0.46 HPMC P.603/PVA ratio and 3.66% EA with a desirability of 0.817. In comparison, the optimal OF-EtOH composition was 0.87 HPMC P.603/PVA ratio and 6.19% EtOH with a desirability of 0.843. The characteristic data for the optimal formulas include: OF-EtOH: weight variation 92.05±4.81 mg, thickness 0.15±0.01 mm, DT 36.11±1.48 sec, and FE 310.33±5.03; and OF-EA: weight variation 93.72±1.50 mg, thickness 0.16±0.00 mm, DT 26.73±3.32 sec, and FE 470.6±37.44. Based on the OF-EtOH FE, the HPMC P.603/PVA ratio had a greater effect compared to the amount of EtOH (p<0.05). The analysis of variance (ANOVA) demonstrated that the amount of EA had a greater impact compared to the HPMC P.603/PVA ratio, with statistical significance (p<0.05). The EtOH cosolvent was preferable to EA based on the LTG solubility and OF dissolution profile. LTG OF had favorable physicochemical properties and showed promise as a rapid-dissolving formulation for therapeutic purposes.   Keywords: Central composite design, cosolvency, disintegration time, folding endurance, oral film.  

Tuberculosis (TB) is a major global health challenge, with high mortality rates. Conventional anti-TB dosage forms, such as tablets are often unsuitable for patients who struggle with swallowing, leading to poorcompliance. Therefore, this study aimed to develop orodispersible film (ODF) containing rifampicin, a widely used anti-TB drug. Rifampicin’s low aqueous solubility poses challenges for its incorporation into ODF andaffects its therapeutic effectiveness. To address these issues, rifampicin was first prepared as nanosuspension and subsequently dried before being formulated into ODF. Nanosuspension was stabilized using polyvinyl alcohol (PVA), poloxamer 188 (POX), and the combination at various concentrations. Nanosuspension was prepared using solvent-antisolvent precipitation followed by sonication and spray-drying. Spray-dried nanosuspension was characterized, and the optimal formula was used in ODF formulation through the solvent-casting method. Formulations PV2 (PVA 0.4%) and POX1 (POX 0.2%) showed the smallest particle sizes at 306±14.01 nm and 291±7.55 nm, respectively. After reconstitution, PV2 maintained particle size comparably to POX1. Spray-dried PV2 nanosuspension exhibited a 21.48-fold increase in saturated solubility compared to the pure rifampicin, and showed superior drug release, with 79% release versus 58% for the standard rifampicin suspension. ODF containing PV2 showed improved organoleptic properties and enhanced drug dissolution (82% vs 56%) compared to original rifampicin ODF. The formulation of rifampicin into nanosuspension stabilized by PVA and POX, followed by spray-drying, significantly improved solubility and drug release profile. This method also enhanced the organoleptic properties and dissolution of rifampicin in ODF, providing a promising strategy to boost rifampicin’s therapeutic efficacy in TB treatment, particularly for pediatric patients.

Background: Breast cancer is a leading cause of morbidity and mortality in women worldwide, with adherence to long-term endocrine therapy proving to be a major clinical challenge. Letrozole (LTZ), a third-generation aromatase inhibitor, is widely used in hormone receptor-sensitive breast cancer; however, its conventional oral tablet form often leads to poor compliance, especially in elderly and dysphagic patients. Objective: The current study aimed to develop and evaluate a patient friendly orodispersible film (ODF) of LTZ to enhance convenience, acceptability, and therapeutic adherence. Methods: LTZ-ODFs were formulated by solvent casting method using hydroxypropyl methylcellulose (HPMC E5) as a film-forming polymer and sodium starch glycolate (SSG) as superdisintegrant and the impact of varying amount of these excipients was evaluated on physicochemical properties and dissolution rate of LTZ. Various formulations (F1-F10) were prepared, the optimized formulation (F3) presented uniform thickness of 0.087 ± 0.013 mm, neutral surface pH (6.9 ± 0.4), excellent folding endurance, and rapid disintegration (14 ± 2 s). Results: In vitro dissolution studies demonstrated more than 95% drug release within 5 min, indicating rapid onset and effective drug dispersion. FTIR spectra confirmed drug excipient compatibility, and stability testing exhibited no significant changes under the accelerated conditions. Conclusion: The developed LTZ-ODF thus may represent a promising alternative delivery system offering improved compliance and enhanced therapeutic efficacy for breast cancer management.

This research work aimed to develop and evaluate an orodispersible film formulation of Naproxen using natural superdisintegrants. Naproxen is a non-selective nonsteroidal anti-inflammatory drug used to reduce pain, fever, and inflammation. Orodispersible films are thin polymeric strips that dissolve rapidly in the mouth without water requirement, offering quick drug delivery and improved patient compliance. The films were prepared by the solvent casting method using hydroxypropyl methylcellulose (HPMC) as the film-forming polymer, natural superdisintegrants for rapid disintegration, and polyethylene glycol as the plasticizer. A total of 10 formulation batches (F1-F10) were prepared with different polymer concentrations and plasticizer ratios. All formulations were evaluated for physical appearance, pH, thickness, weight variation, folding endurance, swelling property, transparency, drug content uniformity, in-vitro disintegration time, in-vitro dissolution studies, and drug release kinetics. The results showed that Naproxen films possessed uniform characteristics with thickness ranging from 0.7 -1.5 mm, good folding endurance, and rapid disintegration within 16-31 seconds. Drug content was uniform with relative standard deviation values below 6%. In-vitro dissolution studies demonstrated more than 90% drug release within 15 minutes for most formulations. The drug release followed zero-order, first-order, Higuchi, and Korsmeyer-Peppas models. These findings suggest that orodispersible Naproxen films represent a promising patient-friendly, fast-acting dosage form that can improve therapeutic effectiveness and patient compliance. Keywords: Orodispersible film, Naproxen, Natural superdisintegrants, Solvent casting, Drug release kinetics.

Objectives Orodispersible films (ODFs) are new-generation dosage forms that increase patient compliance, providing ease of drug administration in many patient groups, such as pediatric, geriatric, and patients with physiological and psychiatric disorders. The aim of this study was to conduct preliminary studies to develop ODF containing the poorly water-soluble and oxidation-sensitive drug desloratadine (DL). Materials and Methods In this study, the formulation and process parameters, as well as the characterization method were investigated using 20 film formulations manufactured by the solvent casting method. The films were characterized in terms of their appearance, mechanical properties, thickness, disintegration time, and content uniformity. Various strategies have been applied to increase the chemical stability of DL in the formulations and, therefore to choose suitable antioxidants, and morphological and compatibility studies using differential scanning calorimetry were performed. For increasing drug loading, different film compositions were also evaluated. Results Among the preliminary formulations tested with a casting height of 400 µm, homogeneous, good mechanical properties with tensile strength values between 6.21-10.34 MPa, flexibility, and ODFs with a disintegration time of less than 60s ODFs were developed. By increasing the solubility of DL in the formulation with the selected components, the drug loading capacity was increased to 3% by the desired level. Conclusion One of the enabling formulations, F20, was particle-free with a suitable thickness uniformity (relative standard deviation =4.6%) and content uniformity (acceptance values =5) films were developed.

Abstract Orodispersible films (ODFs) are an innovative oral drug delivery method benefiting pediatric, geriatric, and non-compliant patients. They are portable, easy to swallow, and enhance bioavailability. Hyaluronic acid (HA) stands out among hydrophilic polymers for oral delivery of antimicrobial agents. This study evaluated the physicochemical properties, in vitro release profile, and antimicrobial/antibiofilm activity of HA-based ODFs combined with the flavonoid morin, known for its antimicrobial properties. Antimicrobial activity and microbial viability were assessed via biomass quantification. The films were thin (12–27 µm), flexible, homogeneous, and mechanically resistant. A burst release of morin was observed, reaching complete release at 210 min. Cytotoxicity analysis confirmed the non-toxic profile, showing cell viability. HA-morin films significantly reduced Streptococcus mutans biofilm mass, viability, and acidogenicity compared to the controls. Findings confirmed the non-toxic, and their significant antibiofilm activity against S. mutans. This innovative mucoadhesive system has potential for managing dental diseases and oral drug delivery. GRAPHICAL ABSTRACT

No abstract available

Rivaroxaban is an anticoagulant and factor Xa inhibitor that acts in deep vein thrombosis. The aim of this study was to prepare a mouth-disintegrating film for the drug to improve its clinical acceptance. As a Biopharmaceutics classification system (BCS) II candidate, the drug requires a significant improvement in solubility to be present as a film. An antisolvent addition method was employed to prepare the cocrystals using gallic acid as a coformer. The optimum nano-crystal formulation (via custom experimental design) was incorporated into a hydroxy propyl methyl cellulose (HPMC) film. The oral films were subjected to physical evaluation, drug content, disintegration time, and drug release studies. Saturation solubility of 0.149 - 1.83 mg/ml was observed. The in vitro release studies showed a drug release of 30±0.14% to 58.2±0.26% at 10min. 49.3±0.18 to 98.7±0.36% at 120min. The optimum formulation solubility and dissolution rate were 1.61mg/ml and 90 %±0.25 at 60min. The X-ray diffraction pattern of the optimum formulation indicated a change in the crystalline nature of rivaroxaban, and the DSC results supported this observation. Films disintegrated in 47s± 0.5 s, and a two-fold increase in drug release from the film (%) was observed in contrast to the pure drug. The nano-cocrystal-incorporated rivaroxaban oral film can be used to improve the therapeutic potential of the drug.

The oral bioavailability of sildenafil citrate is approximately 43%, primarily limited by the low aqueous solubility and first-pass effect. Considering the drug properties and biopharmaceutical considerations, this study aimed to develop an immediate release, taste masked orodispersible film (ODF) of sildenafil citrate for the efficient management of pulmonary arterial hypertension (PAH). The optimization was done by applying 32 full-factorial design. The drug-loaded film was prepared and evaluated for the physical and mechanical parameters like; thickness, disintegration time, tensile strength, elongation, swelling index, content uniformity, disintegration and in vitro drug release in pH 6.2 stimulated salivary fluid. The FTIR and DSC data proved excellent compatibility between the drug and polymers used. The time taken for disintegration by the optimized film was about 62.66 s, while the drug release was observed ~ 96% in 10 min. Pharmacokinetic studies exhibited better sildenafil plasma level (p < 0.05) and Cmax (p < 0.001) of orally disintegrating film which is significantly higher than the oral drug solution. The AUC0–8 (24874.425 ± 1234.45 ng. h/mL) in the oromucosal application was 1.2-fold more (p < 0.0001) than the control. The presence of sweetening and flavoring agents in the formulation masked the drug bitterness, resulting in a higher intake of the formulation in rats compared to the unmasked drug solution, as observed with in vivo taste masking studies. The importance of ODF as a feasible, effective, and optimal approach for delivering sildenafil citrate via oromucosal administration for the treatment of PAH was successfully highlighted by these results.

Orodispersible films (ODFs) have emerged as an advanced and patient-friendly delivery system due to ease of administration, improved patient compliance, quick release and taste-masking of active pharmaceutical ingredients. This research reports the preparation of the ODF containing eugenol and borax (EB-ODF) by a solvent casting technique for treating mouth ulcers. The EB-ODF consisted of Kollidon® VA 64 and hydroxypropyl methylcellulose (HPMC-K250) as the film formers where eugenol and borax were loaded. The thickness of the EB-ODF obtained was 0.119 ± 0.001 mm and the tensile strength was 13.1 ± 1.1 N/mm2 (p > 0.05). The prepared films disintegrated in the oral cavity within 30 s and over 90 % of the eugenol was released from the film in the first 5 min. Furthermore, the combined application of eugenol and borax, loaded in EB-ODF, displayed notable synergetic antibacterial property against both gram-negative and gram-positive bacteria. In an in-vivo study on a rat model with chemical burn-induced oral ulcers, the EB-ODFs treatment group had a 100 % reduction in ulcer area (p > 0.05) after 10 days of treatment and demonstrated a 38.7 % higher reduction in oral ulcer area compared to the Dingpeng Cream treatment group (p < 0.0001). The EB-ODF treatment group The EB-ODF showed minimal oral irritation, scoring only 1 point and a 65 % preference in the taste tests (p < 0.0001). In summary, EB-ODF had successfully overcome the poor palatability of commercially available formulation and provided notable potential for further ulcer treatment development.

In recent years there has been a trend towards creating innovative and patient friendly drug delivery systems which are tailored to each consumer for ensuring drug safety, stability and acceptability. The creation of orodispersible films (ODFs) offers increased comfort and flexibility making it one of the most innovative and promising strategy in drug safety. The film dissolve in oral cavity in few seconds when mixed with saliva. The ODFs can taken with ease and does not require water for administration. ODFs are gaining popularity due to its advantages over other orally administered dosage forms. ODFs offer positive attribute in its ability to customise dosage needs for specific patient population such as Pediatric, elderly, and immobile patients. The purpose of this review paper is to provide information on composition, manufacturing, and characterization of ODFs. The review also provides an overview of polymer used along with the potential drug candidates and focused in printing technology for future market potential. The review suggested that the ODFs is an emerging drug delivery technology for improving patient compliance.

An innovative pharmaceutical form for administering melatonin, based on starch orodispersible fi lm (ODF), was designed and prepared. The composition of the ODF included starch as the polymer matrix, the active drug melatonin, and a plasticizer. Melatonin, a natural hormone produced by the pineal gland in the brain, can be absorbed by passive diffusion across the mucous membrane, resulting in improved bioavailability when compared to conventional oral administration. This study shows a simple and ef fi cient method for preparing melatonin-loaded orodispersible fi lms with a physically stable and commercially viable matrix, suitable for use in the pharmaceutical industry. The fi lms were prepared by treating the starch with microwave irradiation, followed by plasticization with glycerol, melatonin loading and drying by solvent casting. Mechanical tests showed the fi lms ’ robustness, with a modulus of approximately 97 MPa, indicating good handling properties. Moisture uptake analysis showed fast water absorption, reaching about 150% within 2 min, indicating its fast oral disintegration potential. Disintegration tests in arti fi cial saliva and dissolution studies indicated the release of the drug in minutes, indicating the potential properties of the fi lm for oral drug delivery. To the best of our knowledge, there is no melatonin ODF based on starch described in the literature.

Orally-dissolving films, sometimes called orodispersible films (ODF), are a type of oral solid dosage form that dissolves quickly in the mouth without chewing or drinking liquids. These innovative pharmaceutical formulations have attracted a great deal of attention due to their exceptional ability to improve patient compliance and convenience, especially in children, the elderly, and patients with dysphagia, who may have trouble swallowing conventional solid dosage forms. The main goal of orodispersible films is to provide a rapid and effective drug delivery through the oral mucosa. This method of administration has several advantages, such as increased bioavailability, rapid action, and low first-pass metabolism. Orodispersible films have shown effectiveness in the treatment of a wide variety of ailments including mouth ulcers, allergic diseases, cold and cough, sore throat, nausea and restlessness. In the field of pharmacological intervention, these thin, flexible films, designed to quickly disintegrate upon contact with saliva, offer a viable therapeutic strategy. Plasticizers, medicines and organoleptic chemicals are among the substances that are used during the manufacturing of the film. These elements are essential to the normal structure and effectiveness of the film. For example, plasticizers are compounds that are added to film materials to improve their flexibility and toughness. They function by reducing the tension between polymer chains, thereby increasing the film's elasticity and resistance to cracking or breaking. On the other hand, drugs are incorporated into the film structure to accomplish certain therapeutic goals. The purpose of this study is to provide an in-depth review on the fundamental concepts and processes that govern the formulation and evaluation of film, as well as examine the critical factors involved in the packaging process.

Orodispersible films (ODFs) have emerged as innovative pharmaceutical dosage forms, offering patient-specific treatment through adjustable dosing and the combination of diverse active ingredients. This expanding field generates vast datasets, requiring advanced analytical techniques for deeper understanding of data itself. Machine learning is becoming an important tool in the rapidly changing field of pharmaceutical research, particularly in drug preformulation studies. This work aims to explore into the application of machine learning methods for the analysis of experimental data obtained by ODF characterization in order to obtain an insight into the factors governing ODF performance and use it as guidance in pharmaceutical development. Using a dataset derived from extensive experimental studies, various machine learning algorithms were employed to cluster and predict critical properties of ODFs. Our results demonstrate that machine learning models, including Support vector machine, Random forest and Deep learning, exhibit high accuracy in predicting the mechanical properties of ODFs, such as flexibility and rigidity. The predictive models offered insights into the complex interaction of formulation variables. This research is a pilot study that highlights the potential of machine learning as a transformative approach in the pharmaceutical field, paving the way for more efficient and informed drug development processes.

No abstract available

Orally fast-dissolving medicine delivery techniques are increasingly common at present. Due to the desire for these delivery systems, oro-dispersible film (ODF) was recently introduced for the delivery of medicines via the oral route. Most of drugs are delivering through oral route in the form of tablets, capsules and liquids, because they are simple to make and have a greater level of patient compliance. But these conventional dosage forms have many problems including big size of dosage form, and fear of chocking. Oral rapid disintegrating/oro-dispersible drug delivery systems were created to tackle such issues. Fast dissolving films were invented for the patients who have swallowing issues with conventional/traditional oral solid dosage forms. They also have a quick onset of effect, taking only a few seconds, because the drug is absorbed directly from the injection site to the systemic circulation, avoiding first-pass metabolism. In the preparation of films, polymers, surfactants, flavoring agents, coloring agents, sweetening agents, saliva stimulating agents, drug, and plasticizer are used. The drug incorporated in ODF should have pleasing taste, low molecular weight, high stability, and high aqueous solubility. Solvent and semisolid casting, hot melt extrusion, and rolling techniques are routinely used to prepare ODFs. Thickness, loss on drying, tensile strength, and elongation percentage are commonly assessed for evaluating ODFs, as well as their resistance to tearing, weight variation, folding endurance, pH, swelling property, transparency, disintegration, dissolution rate, and stability. The purpose of this review article is to provide a quick overview of ODF delivery systems.

Administration of drugs via the oromucosal route, especially using oral thin films, improves patient adherence compared to conventional oral and injectable methods. However, existing production techniques for oral thin films face considerable challenges in incorporating peptide and protein drugs. This study presents electrospun nanofiber‐based oral thin film as a viable platform for the sublingual delivery of semaglutide. This platform was tested in Göttingen minipigs, which showed a greater response to attenuation of weight gain.

The advancement of the oral route for macromolecules has gained a lot of attention due to its noninvasive nature, safe and challenging in active research but with limited success. Oral administration poses challenges due to poor solubility, short half-life, quick elimination and the physical, chemical and biological barriers of the gastrointestinal tract. Approaches of past for improving oral absorption, such as enhancers, mucoadhesive delivery and enzyme inhibitors have been taken over by novel approaches like advanced liposomes, self-nanoemulsifying drug delivery system, nanoparticles and targeted delivery. Eudratech™ Pep, Peptelligence, Rani Pill and Pharm Film are the emerging technologies for delivering oral proteins and peptide. Calcitonin, semaglutide and octreotide are the peptides available in the market for oral delivery as outcomes of these technologies.

Oral delivery of macromolecules is hindered by enzymatic degradation, poor epithelial permeability, and rapid gastric transit, leading to low bioavailability. Existing permeation enhancers (PEs), such as salcaprozate sodium and sodium caprate, improve absorption but do not fully address proteolytic degradation and require high doses due in part to short gastrointestinal residence times. We developed the Peroral Mucosal Epithelium Absorption Enhancer (PERMEATE) system, an orally administered polymer film designed to adhere to the small intestinal mucosa, maximizing contact between therapeutics, PEs, and the absorptive tissue. Utilizing Synthetic Tissue-Lining (SYNT™) technology, PERMEATE triggers endogenous catalase-dependent dopamine polymerization to form an in situ polydopamine coating, creating a temporary depot that enhances co-localization and prolongs exposure to the absorptive mucosa. We assessed PERMEATE’s potential to enhance the oral bioavailability of semaglutide (SEMA). High-throughput screening using the GI tissue robotic interface system (GI-ORIS) identified glycocholic acid (GCA) and ammonium carbonate (NHCO) as effective PEs when combined with SYNT. Ex vivo studies (n=8–24) and in vivo tests in Sprague-Dawley rats (n=5–11/group) demonstrated a 200-fold increase in bioavailability compared to SEMA alone (P=0.0001) and a 6-fold increase relative to SEMA+PE without SYNT (P=0.0011). In Yorkshire pigs (n=3–4), PERMEATE achieved a 2.4% absolute bioavailability, a 6-fold improvement over SEMA+PE controls (P=0.0316). These results suggest PERMEATE as a promising platform for improving oral macromolecule delivery through enhanced mucosal adhesion and prolonged therapeutic contact, supporting further development for clinical application.

Fast-dissolving oral delivery systems are solid dosage forms, which disintegrate or dissolve within 1 min when placed in the mouth without drinking water or chewing. This facilitates the rapid absorption in the oral cavity and reduces first-pass effects. The aim of this study is to formulate and evaluate the Fast dissolving Oral film of Promethazine hydrochloride as a strong antihistamine which are used to reduce nausea, motion sickness and improved bioavailability of drugs as compared to conventional solid oral dosage forms. The films were prepared Hydroxy propylmethyl cellulose E15 as a film base synthetic polymer and PEG400 (Poly Ethylene Glycol 400) as a plasticizer by solvent casting method. SLS (Sodium Lauryl Sulfate) and MCC (Micro Crystalline Cellulose) used as a surfactant in different concentration. Sucrose used as a sweetening agent and strawberry as a flavoring agent. Films were found to be satisfactory when evaluated for thickness, weight uniformity, in-vitro drug release, folding endurance, drug content and disintegration time. The surface pH of all the films was found to be neutral or minor change. Films in vitro drug release studies also done by using USP dissolution apparatus. The in vitro drug release in optimized formulation F2 was found to be 14.36% in 2 min. The optimized formulation F2 also showed satisfactory pH, drug content (97.41±0.54%), effective in vitro drug release (96.03±0.68% in 16 min), disintegration time of 09 seconds and satisfactory stability.The Promethazine hydrochloride fast dissolving oral film was formulated. The given film disintegrates within nine seconds which release drug rapidly and gives action.

Simple Summary This study explores how semaglutide, a drug extensively and widely used to treat diabetes and obesity, may cause oral side effects, such as dry mouth, by affecting salivary gland function. Based on the available data, we propose that different GLP-1 receptor agonists activate the salivary gland receptor in distinct ways, triggering pathways that regulate secretion and cell protection. Because semaglutide has strong albumin binding, which leads to prolonged receptor activation, it may disturb the rhythmic calcium and cAMP cross-talk essential for normal salivary secretion. Persistent stimulation may cause receptor desensitization, β-arrestin–mediated internalization, and reduced gland responsiveness. Understanding these mechanisms helps explain why some patients experience oral dryness when taking semaglutide. The findings highlight the importance of monitoring oral health and tailoring treatments to improve comfort and safety for people using semaglutide.

No abstract available

The PIONEER REAL Italy study examined the clinical outcomes associated with oral semaglutide in real-world settings. This was a multicenter, prospective, non-interventional, single-arm study in adults with type 2 diabetes (T2D) who were treatment-naive to injectable glucose-lowering medications. Participants initiated oral semaglutide at doses of 3, 7, or 14 mg, and were followed for 34–44 weeks. The primary endpoint was the change in glycated hemoglobin (HbA1c) from baseline to the end of study (EoS). Secondary endpoints were the change in body weight (BW), the percentage of participants attaining HbA1c < 7%, composite endpoints of HbA1c reduction ≥ 1%-point plus BW reduction (≥ 3%/ ≥ 5%), and treatment satisfaction measured using Diabetes Treatment Satisfaction Questionnaires (DTSQ) status. Safety was assessed in participants who received ≥ 1 dose of oral semaglutide. Of 445 eligible participants, 398 completed the study; 351 (78.9%) remained on oral semaglutide at EoS. The median time of treatment follow-up was 40 weeks for each participant. At baseline, participants had a mean (standard deviation [SD]) age of 62.9 (10.2) years, HbA1c of 7.8% (1.3), T2D duration of 8.0 (6.9) years, and BW of 87.8 (19.0) kg. The estimated changes (95% confidence interval) from baseline to EoS in HbA1c and BW were − 0.9%-points (− 1.01 to − 0.82; p < 0.0001) and − 3.8 kg (− 4.45 to − 3.24; p < 0.0001), respectively. At EoS, 65.1% achieved HbA1c < 7%; 25.5% and 19.1% reached HbA1c reduction ≥ 1%-point plus ≥ 3% and ≥ 5% reduction in BW, respectively. DTSQ status improved significantly at EoS (estimated change + 5.24; 95% CI, 5.24 to 6.61, p < 0.0001). Of participants who remained on oral semaglutide at EoS, 72.6% received a 7-mg dose. No new safety signals were observed. In Italy, the real-world clinical outcomes associated with oral semaglutide in adults with T2D complemented the findings from clinical trials. This reassures oral semaglutide usage in routine clinical practice. NCT05230615.

Background Clinical obesity is a prevalent chronic disease, significantly increasing morbidity and mortality while impairing quality of life. As diet and physical activity interventions often prove ineffective in the long term, with increasing use of pharmacotherapy, drug shortages and injection aversion present a challenge. The role of oral semaglutide at a dose of 14 mg (registered for type 2 diabetes) as a treatment for obesity in patients without diabetes remains undefined. Methods In the retrospective real-world study, which included 93 adults without diabetes (57% women, average age 52 years), we assessed whether treatment with 14 mg oral semaglutide over one year is associated with lower body weight, body mass index (BMI), waist circumference, blood pressure, heart rate, and obesity staging according to EOSS. Results Of the 93 subjects recruited, 82 (88%) were receiving oral semaglutide at a dose of 14 mg after one year. After one year of treatment body weight was significantly lower by 5.7% (5.9 kg) in completers, and BMI decreased significantly by an average of 2 kg/m². There was also a significant reduction in waist circumference by 5.5 cm and a decrease in EOSS score by 0.1. Clinically significant weight loss was achieved in 46% of all participants, with rare individuals experiencing a decrease of ≥ 15%. Adverse effects were mostly mild, with nausea reported by 23% and vomiting and diarrhoea by 12% of participants. Conclusions Obesity treatment with oral semaglutide at a dose of 14 mg showed marked interindividual variability, with approximately half achieving clinically significant reductions – mostly under 10%. Although less effective than injectable therapy, oral semaglutide at a dose of 14 mg had a favorable safety profile and may be suitable in selected clinical scenarios.

This real‐world, retrospective cohort study aimed to assess the efficacy, safety and tolerability of oral semaglutide—the first GLP‐1 receptor agonist available in oral form—in patients aged 65 years and older with type 2 diabetes mellitus (T2DM).

BACKGROUND Cardiovascular disease remains a leading cause of morbidity and mortality in type 2 diabetic mellitus (T2DM) patients. While injectable GLP-1 RAs have demonstrated efficacy in reducing cardiovascular risk, an oral formulation of semaglutide was developed to improve accessibility and treatment adherence, however, its therapeutic potential has yet to be fully elucidated. This meta-analysis evaluates the efficacy of oral semaglutide on cardiovascular outcomes to better inform clinical decision-making. METHODS A systematic search was conducted in major databases for randomized controlled trials (RCTs) up to May 2025, with a primary outcome of cardiovascular events, expanded outcomes included nonfatal stroke, death from cardiovascular cause, and nonfatal myocardial infarction, and the secondary outcome was all-cause mortality. Statistical analysis was performed using RStudio, with heterogeneity assessed via I2 statistics. RESULTS A total of 13,875 patients were included, of whom 6935 received oral semaglutide and 6940 received placebo from the 5 eligible studies. A significant difference was observed for cardiovascular events with a risk ratio (RR) of 0.86 (95 % CI: 0.78-0.95; p = 0.0029; I2 = 0 %) and hazard ratio (HR) of 0.85 (95 % CI: 0.77-0.95), respectively. In contrast, no significant difference was found for nonfatal stroke, all-cause mortality, death from cardiovascular causes, and nonfatal myocardial infarction. CONCLUSION The meta-analysis revealed that oral semaglutide was cardioprotective in T2DM patients with consistent reductions in cardiovascular event risk. However, the lack of significance in the remaining outcomes underscores the need for further investigation.

Background/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is an important common comorbidity in subjects with type 2 diabetes, and liver fibrosis is a factor directly related to its prognosis. Glucagon-like peptide-1 receptor agonists are useful treatment options for MASLD; however, the efficacy of oral semaglutide in treating liver steatosis/fibrosis has not been fully elucidated. Methods: A secondary analysis of a multicenter, retrospective, observational study investigating the efficacy and safety of oral semaglutide in Japanese subjects with type 2 diabetes in a real-world clinical setting (the Sapporo-Oral SEMA study) was conducted. Subjects in the original cohort were divided into groups as follows: subjects with suspected MASLD (alanine aminotransferase > 30 U/L) were placed in an overall group; a subpopulation from an overall group at high risk for hepatic fibrosis (fibrosis-4 (FIB-4) index ≥ 1.3 or platelet count < 200,000/µL) was placed in a high-risk group; and the remaining subjects were placed in a low-risk group. Changes in the hepatic steatosis index and FIB-4 index after oral semaglutide induction were explored using a paired t-test or the Wilcoxon signed-rank test. Results: Overall, 169 subjects (including 131 that switched from other medications) were analyzed, and 67 and 102 subjects were selected for the high-risk and low-risk groups, respectively. Oral semaglutide significantly improved the hepatic steatosis index (from 46.1 to 44.6, p < 0.001) and FIB-4 index (from 1.04 to 0.96, p < 0.001) as well as several metabolic parameters in all cohorts. The efficacy of semaglutide in treating liver fibrosis was confirmed by the addition of, and switching from, existing agent groups. Furthermore, improvement in the FIB-4 index was significantly negatively correlated with the baseline FIB-4 index. Conclusions: The induction of oral semaglutide might be a useful treatment option for subjects with type 2 diabetes at high risk for liver fibrosis, even when switching from conventional medications for diabetes.

To investigate the effects of once‐daily oral semaglutide 50 mg on energy intake, appetite, control of eating and gastric emptying.

BACKGROUND We assessed the efficacy and safety of the oral glucagon-like peptide-1 analogue, semaglutide 50 mg, taken once per day versus placebo for the treatment of overweight or obesity in adults without type 2 diabetes. METHODS This randomised, double-blind, placebo-controlled, phase 3, superiority trial enrolled adults with a BMI of at least 30 kg/m2, or at least 27 kg/m2 with bodyweight-related complications and comorbidities, without type 2 diabetes. The trial was done at 50 outpatient clinics in nine countries across Asia, Europe, and North America. Participants were randomly allocated (1:1) via an interactive web-response system to oral semaglutide escalated to 50 mg, or visually matching placebo, once per day for 68 weeks, plus lifestyle intervention. Group assignment was masked for participants, investigators, and those assessing outcomes. Coprimary endpoints were the percentage change in bodyweight and whether participants reached a bodyweight reduction of at least 5% at week 68 for oral semaglutide 50 mg versus placebo, assessed regardless of treatment discontinuation or use of other bodyweight-lowering therapies (an intention-to-treat analysis). Safety was assessed in participants who received at least one dose of trial drug. This trial, registered with ClinicalTrials.gov (NCT05035095), is now complete. FINDINGS From Sept 13 to Nov 22, 2021, 709 participants were screened, of whom 667 were randomly assigned to oral semaglutide 50 mg (n=334) or placebo (n=333). The estimated mean bodyweight change from baseline to week 68 was -15·1% (SE 0·5) with oral semaglutide 50 mg versus -2·4% (0·5) with placebo (estimated treatment difference -12·7 percentage points, 95% CI -14·2 to -11·3; p<0·0001). More participants reached bodyweight reductions of at least 5% (269 [85%] of 317 vs 76 [26%] of 295; odds ratio [OR] 12·6, 95% CI 8·5 to 18·7; p<0·0001), 10% (220 [69%] vs 35 [12%]; OR 14·7, 9·6 to 22·6), 15% (170 [54%] vs 17 [6%]; OR 17·9, 10·4 to 30·7), and 20% (107 [34%] vs 8 [3%]; OR 18·5, 8·8 to 38·9) at week 68 with oral semaglutide 50 mg versus placebo. Adverse events were more frequent with oral semaglutide 50 mg (307 [92%] of 334) than with placebo (285 [86%] of 333). Gastrointestinal adverse events (mostly mild to moderate) were reported in 268 (80%) participants with oral semaglutide 50 mg and 154 (46%) with placebo. INTERPRETATION In adults with overweight or obesity without type 2 diabetes, oral semaglutide 50 mg once per day led to a superior and clinically meaningful decrease in bodyweight compared with placebo. FUNDING Novo Nordisk.

Background Porphyromonas gingivalis is a key pathogen in periodontitis, which involves inflammation and alveolar bone loss. An imbalance of cytokines and growth factors contributes to disease progression. Rice husk liquid smoke has shown potential antibacterial and anti-inflammatory properties. Objective This study aimed to formulate and characterize an oral thin film (OTF) containing rice husk liquid smoke and evaluate its antibacterial activity and biological effects in a periodontitis model. Methods OTFs were prepared using hydroxypropyl methylcellulose, gelatin, sorbitol, and rice husk liquid smoke via solvent casting. The OTF were characterized for weight, thickness, swelling, disintegration, dissolution, and antibacterial activity against Porphyromonas gingivalis. For in vivo testing, periodontitis was induced in 28 Wistar rats. OTFs were applied to periodontal pockets. Mandibular tissues were collected on days 2 and 7 for immunohistochemical analysis of IL-6, IL-10, FGF-2, and BMP-2 expression. Results The OTFs showed favorable physical properties, including low weight, appropriate thickness, and faster disintegration and dissolution times (p < 0.05). Both OTF and blank films inhibited Porphyromonas gingivalis growth. OTF treatment significantly decreased IL-6 and increased IL-10, FGF-2, and BMP-2 expression at both time points (p < 0.05), indicating reduced inflammation and enhanced tissue regeneration. Conclusion The OTF containing rice husk liquid smoke exhibited strong antibacterial and immunomodulatory effects, suggesting its potential as a novel therapeutic strategy for periodontitis.

The current research work aimed to prepare an optimized and evaluate fast-dissolving oral thin film of Apixaban using polyvinyl alcohol as a film former. The oral thin film of Apixaban enhances the solubility, bioavailability, and therapeutic efficacy in thrombus, pulmonary embolism, and venous thromboembolism. The chemical compatibility and thermal analysis were investigated with the help of FTIR, and DSC. The optimization was performed with the Box-Behnken design. The concentrations of film former (PVA: X1), plasticizer (PEG 200: X2), and superdisintegrant (cross povidone: X3) were considered as independent factors and the critical quality attributes for the oral films are disintegration time, dissolution, and folding endurance. The ANOVA comprised of Quadratic model which predicted p-values of 0.0039, 0.0105, and 0.0020 significant. The scanning electron microscopy assessed the texture of the film. An optimized batch P6 disintegrated within 19 seconds, released the drug (99.07 %) within 10 min and had a folding endurance of 116. The results conclude that optimized batch P6 of oral thin film of Apixaban significantly minimizes the deep vein thrombosis, pulmonary embolism, and venous thromboembolism due to fastest onset of action and improved solubility. Thus, the complications associated with the clotting of blood is sharply reduces.

The present study aimed to develop an ondansetron microemulsion and incorporate it into an oral thin film. In the design of experiments, a central composite design was utilized to optimize the formulations, focusing on the concentrations of hydroxypropyl methylcellulose (HPMC K15) (X1) and HPMC K4 (X2) as independent variables. The optimized batch designated as FB-1, exhibited a drug content of 101±0.5%, a film weight of 49.8±0.8mg, a minimum disintegration time of 47±0.05 seconds, a thickness of 0.12±0.2mm, and a pH of 6.8 ±0.05, along with desirable mechanical properties, including a tensile strength of 150g/cm². Characterization of the optimized film includes FTIR, DSC for drug interaction, SEM for morphology, and evaluations of in vitro drug release and ondansetron loading effectiveness. The optimized batch exhibited a remarkable drug release profile, achieving approximately 88.83% release at the 5 min mark. This rapid dissolution continued, surpassing 95 % within the first 10 min, demonstrating the highest dissolution rate observed. The developed ME-loaded OTFs significantly enhanced drug release compared to the marketed film Vomikind-Fast strip 4mg (Mankind Pharma) showed a 64% release at 5 min and 65% at 10min, while Emefilm 4mg (Delvin Formulations) had a release rate of 64% at 5 min and 68% at 10min. By improving the solubility and bioavailability of ondansetron, this microemulsion-embedded film technology offers a dosage form that is both easy to administer and improves compliance among patients.

Bad breath is a health issue characterized by unpleasant breath originating from the oral cavity, often caused by bacterial growth. One significant contributor to bad breath is the proliferation of bacteria responsible for dental caries, namely Streptococcus mutans (S. mutans). Lemongrass (Cymbopogon citratus (DC). Stapf), known for the antibacterial properties, has long been used as a traditional remedy for treating bad breath. Therefore, this study aimed to develop Oral Thin Film (OTF) preparation containing lemongrass extract as one of the solutions to reduce bad breath. Lemongrass leaves were extracted using 96% ethanol through maceration. OTF preparation optimization was carried out by solvent casting method using 3% gelatin and variations of Hydroxy Propyl Methyl Cellulose (HPMC) and corn starch in 5 formulas (F1-F5), namely 1:0, 3:1, 1:1, 1:3, and 0:1, respectively. The evaluation criteria for the OTF included organoleptic test, weight uniformity, film thickness, pH, folding resistance, color assesment, disintegration time and antibacterial efficacy against S. mutans using the disc diffusion method. Stability tests were conducted at different temperatures (25oC and 40oC) over a period of 3 months. The OTF preparation had a uniform film weight, film thickness in the range of 0.2240 - 0.3415mm, pH value at 6.12-6.36, folding resistance at 339.67 - 579.50 times, and disintegration time at 60-105 s. Despite exhibiting good stability over a 3-month period, all films demonstrated weak antibacterial activity, as shown by inhibition zone diameters ranging from 7.8 to 8.7mm. The preparation of OTF loaded with Cymbopogon citratus leaf ethanolic extract yielded excellent physical characteristics.

Objective: This study aimed to develop and optimize an Oral Thin Film (OTF) formulation of escitalopram oxalate to enhance patient compliance, improve drug acceptability, and facilitate rapid systemic absorption. Methods: A Central Composite Design (CCD) under Response Surface Methodology (RSM) was employed to optimize the formulation. Polymer (300–500 mg) and plasticizer (100–300 mg) concentrations were selected as independent variables, and their effects on critical response parameters—tensile strength, folding endurance, disintegration time, and dissolution rate-were evaluated. The optimized OTF was characterized for thickness, disintegration, and dissolution behaviour. Results: The optimal polymer and plasticizer concentrations were identified as 400 mg and 220 mg, respectively, yielding desirable film properties. The OTF thickness ranged from 0.48 to 0.57 mm, with formulations between 0.50 and 0.55 mm exhibiting the most favorable dissolution and disintegration profiles. The optimized OTF exhibited a tensile strength of 15.3 N/mm², folding endurance of 159 folds, and a disintegration time of 73 sec. Dissolution studies demonstrated 98% drug release within 10 min, confirming rapid dissolution for a fast onset of action. Conclusion: The study successfully developed an optimized OTF formulation of escitalopram oxalate, supporting the global shift toward patient-centric drug delivery. The formulation enhances therapeutic outcomes by ensuring rapid systemic absorption and improved patient adherence.

Vaccines rely on a global cold chain to maintain vaccine potency throughout the product life cycle. Existing vaccine thermostabilization methods like lyophilization and spray-drying impart significant stress on the vaccine, reducing its potency. Therefore, dissolvable oral thin films (OTFs) have emerged as an alternative thermostabilizing vaccine delivery platform wherein the vaccine is immobilized in a polymer-sugar matrix and administered to the oral mucosa. Herein, we demonstrate the feasibility of incorporating a model adenovirus vector into an OTF (Ad5 OTF) using a simple one-hour solvent casting process, and we demonstrate retention of the adenovirus infectious titer during storage, as assessed by flow cytometric titering. Increasing Tris buffer concentration and changing the surfactant from a nonionic Tween 80 to a zwitterionic poly(maleic anhydride-alt-1-octadecene) substituted with 3-(dimethylamino)propylamine (PMAL) and increasing its concentration improved the six-day ambient temperature stability by nearly 4-fold. A 23 full factorial design of experiment investigating the influence of trehalose, PEG, and PMAL concentration demonstrated that PMAL and trehalose concentration have the greatest impact on stability of Ad5 OTFs, improving the six-day ambient temperature stability by 250-fold, compared to the first formulation evaluated herein. The thermal stabilization of Ad5 OTFs prepared with a simple one-hour casting process demonstrates the scale-up and scale-out potential for this OTF formulation as a vaccine delivery platform, improving the accessibility of vaccines.

The aim of the current study was to formulate and evaluate dompridone nanoparticles and loaded in oral fast dissolve fi lm, for enhance the solubility of poor water soluble dompridone by nanoparticles and fasten the action by prepared as oral thin fi lm and also to improve patient compliance. Domperidone is the recommended medication for nausea and vomiting brought on by viral infections, chemotherapy, migraines, and food poisoning. Domperidone nanoparticles were made using two type of polymers (hydroxypropyl methylcellulose HPMC-K15 and methylcellulose MC-A4C) in a range of ratios (1:1, 1:2, and 1:3) drug:polymer ratio by solvent antisolvent technique. In nanoparticle formulation, HPMC-K15 and MC-A4C were selected due to their advantageous characteristics: they are water-soluble, form robust fi lms, are biologically compatible, and have a proven history in pharmaceutical applications. The prepared formula undergoes to characterization for particle size, PDI, FESEM and x-ray diffraction. The results obtain show all formulas within nano size range and monodisperse. The X-ray powder diffraction examination showed that the dompridone had changed from a crystalline to amorphous state. Following that, the optimum nanoparticles formula was used to prepare the oral fi lm using the technique of solvent casting with HPMC E15 acting as a fi lm forming agent and glycerin as a stabilizer. The prepared oral fi lm, appear as a white, opaque, soft thin fi lm with drug content 98.85 ± 1.13 %, and a good folding endurance. Invitro release of drug show, the cumulative proportion of dopamine released from the fi lm containing the nanoparticles was 43 %, while only 21 % for fi lm consist of pure dompridone, at 2 min.

Starch is a natural biopolymer used as a film-forming polymer on oral thin film (OTF). Its solubility can increase by modifying enzymes to form maltodextrin (MDX). Sorghum is a potential plant because it contains relatively high starch, 72.3-75.1%. The concentration of film-forming and plasticizers in OTF will significantly affect its disintegration and mechanical properties. This study aimed to obtain the optimal formula for OTF cetirizine HCl based on MDX-sorghum as a film-forming and triethyl citrate as a plasticizer using the Response Surface Methodology (RSM). Sorghum starch was enzymatically modified and characterized physically and mechanically. The formula is optimized based on the disintegration and mechanical properties of the film on the contour plot using Central Composite Design (CCD) in RSM. The percentage error between the predicted and actual values in the response validates the suggested model. The results showed that the production of MDX-sorghum was successful with a characteristic value of dextrose equivalent (DE) 6,3±0,13; swelling power of 2.87; solubility of 52.9%; and a yield of 86.71%. Response data from the 14 formulas obtained include disintegration time of 85-172 seconds, elongation 64.86-109.32%, and tensile strength from 1.4 to 3.57 MPa. The optimal formula suggested a concentration of 4.56% MDX-sorghum and 10% triethyl citrate, with desirability of 0.87. The model validation results show an error percentage of <5%, so the suggested model can be accepted.

Background Oral Thin Film (OTF) is an emerging approach for oral drug delivery but still there exists a scarcity of evidence for formulation optimization techniques. Herein, we aim to develop OTFs optimized by the QbD approach. Materials and Methods OTFs were prepared by solvent casting method using Amlodipine as an active ingredient and excipients such as Pectin, Aspartame, Tween 80, and Glycerine. The developed formulation was optimized using QbD software Design Expert version 8.0.4, USA. The independent variables of the experiment were selected as A-pectin, B-Tween-80, and C-glycerine, and the dependent variables were R1-tensile strength (kg/cm2), R2-permeation rate (μg/cm2/hr), R3-disintegration time (in a sec). Finally, the software suggested optimized formulation based on a desirability value closer to 1. Results The optimized oral films were comparatively evaluated and characterized by various techniques. The drug release was found to be ~96% at 10 min for OTFs and ~94% at 20 min for oral fast-dissolving tablets. The amlodipine was scanned in the UV range of 200 to 400 nm and the λmax was observed to be at 240±2 in a Phosphate of pH 6.8. Conclusion All results are found satisfactory and well within the acceptance range. This ensures that similar formulations can be optimized by using this technique in the future.

Daun saga rambat (Abrus precatorius L.) dapat menjadi alternatif pada pengobatan sariawan yang biasa dimanfaatkan oleh masyarakat secara turun – temurun dengan cara ditumbuk sampai lumat dan kemudian ditambah air matang untuk dikumur atau bahkan diminum. Daun saga rambat memiliki aktivitas sebagai antijamur, karena tanaman ini mengandung senyawa metabolit sekunder berupa flavonoid, saponin, alkaloid dan steroid yang dapat menghambat pertumbuhan jamur Candida albicans. Penelitian ini bertujuan untuk menentukan variasi polimer HPMC dan PEG 400 yang menghasilkan mutu fisik terbaik dari sediaan oral thin film ekstrak daun saga (Abrus precatorius L.) yang memenuhi syarat mutu. Sediaan dibuat sebanyak 4 formula dengan perbedaan konsentrasi pada PEG 400 yaitu F1 dengan konsentrasi 5%, F2 dengan konsentrasi 10%. F3 dengan konsentrasi 15%. Dan F4 dengan konsentrasi 20%. Hasil penelitian menunjukkan variasi konsentrasi berpengaruh terhadap mutu sediaan oral thin film, formula 3 merupakan formula formula terbaik berdasarkan uji waktu hancur (48 detik), uji ketahanan lipat (201,2) dan persen pemanjangan (85,71%).

BACKGROUND Cardiovascular diseases, including hypertension, are the prominent source of death globally. High blood pressure is responsible for heart failure and also damages the vital organs of the body, which also creates mortality. The activation of the sympathetic nervous system in the primary sunrise period is a highly critical condition, and several persons have lost their tissue due to the unavailability of medicine at this time. OBJECTIVE The present research deals with the progress of fast-dissolving oral thin film (OTF) of Ambrisentan for the prevention and cure of hypertension. METHODS The OTF was established using the solvent casting method. The compatibility of Ambrisentan with film former HPMC E15 was checked with FTIR and DSC. The optimization was assessed using the design of the experiment using 32 Box-Behnken designs. The independent parameters were filmed former (X1: HPMC E15), plasticizer (X2: PEG 400), and super disintegrant (X3: cross povidone) and dependable parameters were disintegration time (Y1) and dissolution release (Y2). RESULTS The optimized batch F7 showed the least disintegration time (9 sec), folding endurance of (99), content uniformity (98.57 %), pH (6.4), and dissolved within 5 min. The scanning electron microscopy confirmed the evenness and smoothness of the film with a particle size of 10 μm. Patent related with OTF (Indian- 202321050359), US (11701339). CONCLUSION The investigation indicated that fast dissolving oral thin film of Ambrisentan improves the solubility and therapeutic efficacy in the prevention and treatment of cardiovascular complications. The prompt release of Ambrisentan minimizes the mortality associated with heart attack and hypertension.

Objective: The aim of this study was to formulate an oral thin film strip (OTFS) contained the red dragon fruit peel (RDFP) ethanol extract (Hylocereus polyrhizus) and evaluate the characteristic, stability and antibacterial activity against Streptococcus mutans (S. mutans). Methods: The film was made using the solvent casting method by adding a variety of concentration ethanol extract of red dragon fruit peel (5%, 10%, and 15%). The films were evaluated in organoleptic test, weight, thickness, pH, disintegration time, folding endurance, stability test and antibacterial activity. Results: The results showed that the film provided a distinctive color, aroma, and taste of the extract. The result of film evaluation had weight between 0.07-0.21 g, thickness between 0.10-0.20 mm, pH between 5.70-5.99, disintegration time between 34.99-49.13 s, and folding endurance between 321.00-812.83 times. The films were stable for 2 mo at a variety storage temperature (4±2 ℃, 28±2 ℃, and 40±2 ℃). The films showed antibacterial activity for 5%, 10% and 15% with the diameter of inhibition 8.5 mm, 10.8 mm, and 12.9 mm, respectively. Conclusion: Ethanol extract of RDFP can be utilized as a mouth freshener film that is stable for 2 mo and has antibacterial activity against S. mutans.

This comprehensive review delves into the recent advancements and diverse applications of oral thin film (OTF) technology in the field of pharmaceuticals. The aim is to provide a thorough exploration of the evolution of OTFs, their unique characteristics, and their expanding role in drug delivery systems. A systematic analysis of the literature was conducted to gather information on the formulation techniques, properties, and challenges associated with OTFs. Additionally, recent developments, innovations, and future trends in OTF technology were examined to understand the dynamic landscape of this drug delivery system. The review highlights the key properties of OTFs, including rapid disintegration, enhanced bioavailability, and patient-centric advantages. Various manufacturing techniques, such as solvent casting, hot melt extrusion, and 3D printing, were explored for their impact on OTF formulation. Challenges, including stability issues and taste masking complexities, were identified. Recent innovations, such as nanotechnology integration, personalized medicine applications, and the use of digital health platforms, showcase the ongoing efforts to overcome these challenges. Oral thin film technology stands at the forefront of pharmaceutical innovation, offering a patient-friendly and adaptable drug delivery system. As evidenced by recent developments, the integration of advanced technologies, personalized medicine approaches, and sustainable practices positions OTFs as a transformative force in the future of drug delivery. The exploration of these advancements and applications contributes to a deeper understanding of the potential impact of OTF technology on healthcare.

Background: Fast dissolving oral thin films (FDTFs) offer a promising delivery platform for drugs with poor aqueous solubility and bioavailability. Eugenol, a natural compound with diverse pharmacological properties, faces challenges in oral delivery due to its low aqueous solubility and high volatility. Objective: This study aimed to develop a fast dissolving oral thin film formulation of eugenol to enhance its bioavailability and facilitate convenient administration. Methods: The FDTFs were prepared using a solvent casting method with hydroxypropyl methylcellulose (HPMC) and polyethylene glycol (PEG) as film-forming agents. The formulations were optimized based on criteria such as film thickness, folding endurance, tensile strength, disintegration time, and drug release profile. Characterization studies to evaluate the physicochemical properties of the optimized formulation. Results: The optimized eugenol-loaded FDTFs exhibited desirable mechanical properties, rapid disintegration, and enhanced drug release compared to conventional dosage forms. Conclusion: The developed fast dissolving oral thin film of eugenol holds promise as a novel delivery system for enhancing the bioavailability of eugenol.

HIV infections among children have been on the decline since the introduction of infant HIV prophylaxis regimens including the HIV reverse transcriptase inhibitor, zidovudine (ZDV). This makes adherence to ZDV and other HIV medications paramount for the survival of young infants and children across the globe. However, the large dose volume and extremely bitter taste of ZDV often results in infants spitting up the medication, resulting in inaccurate dosing. Inclusion of ZDV into an oral thin film (OTF) would reduce the dose volume required, thus improving adherence to the medication regimen. To overcome the poor taste of ZDV, we created encapsulated ZDV (eZDV) formulations via spray-drying and evaluated polymer selection and ZDV particle size as potential avenues for effectively reducing the release of ZDV in simulated salivary fluid (SSF). The combined use of Eudragit E PO (EPO) and ethylcellulose (EC) was found to be the most effective polymer coating for reducing the release of ZDV. The optimal formulation ratio was determined to be 5:20:75 (EC:EPO:ZDV) to maintain high drug load while still reducing the dissolution of ZDV in SSF. Additionally, mortar-and-pestling ZDV prior to spray drying allowed for less variability and a more homogenous spread of eZDV throughout an OTF. These factors ultimately resulted in eZDV loaded OTFs that were able to successfully reduce the release of ZDV in SSF below its taste detection threshold.

Abstract Nutraceuticals have been gradually accepted as food ingredients which can provide health benefits and protection against several diseases. However, most nutraceuticals are susceptible to the changes in the external environment, resulting in a poor stability and absorption. One such relatively novel, inventive, and patient-centered innovation routed in this direction is oral thin film (OTF). OTFs are ultra-thin, stamp-sized, portable and patient-centric formulations with no need for water. This route allows for the absorption of drugs through the oral mucosa, effectively bypassing hepatic first-pass metabolism in the liver and avoiding degradation or metabolism within the gastrointestinal tract. Accordingly, OTFs hold tremendous potential in gaining patient compliance, convenience and pharmacotherapy. This review highlights the utilization OTFs for nutraceutical delivery, including their types, preparation methods and the potential of OTFs as carriers for delivering plant extracts, bioactive molecules, vitamins, proteins and microorganisms. Moreover, the quality evaluation methods and applications of OTFs are summarized.

The present study aimed to evaluate the stability profile of Betahistine Dihydrochloride in its pure active pharmaceutical ingredient (API) form and as an Oral Thin Film (OTF) formulation through forced degradation studies under various stress conditions. Degradation studies were performed under acidic (0.1N HCl), alkaline (0.1N NaOH), oxidative (3% H₂O₂), and thermal (100°C) conditions to assess the intrinsic stability of the drug and to establish the stability-indicating capability of the developed analytical method. Samples were analyzed at predetermined time intervals up to 48 hours. The results demonstrated that Betahistine Dihydrochloride is susceptible to all applied stress conditions, with oxidative degradation showing the highest extent of degradation (20.76% for API and 13.23% for OTF at 48 hours). Acidic and thermal stress also produced significant degradation, with 17.64% and 18.23% degradation observed for the API, respectively. Alkaline degradation was comparatively moderate (16.56% at 48 hours). In all stress conditions, the OTF formulation exhibited lower degradation than the pure API, indicating a protective effect of the polymeric film matrix. Chromatographic analysis confirmed clear separation of degradation products from the parent drug peak, demonstrating the specificity and stability-indicating nature of the analytical method. Overall, the study concludes that Betahistine Dihydrochloride is particularly susceptible to oxidative and thermal stress, while the OTF formulation offers improved stability compared to the pure drug. These findings emphasize the importance of appropriate storage conditions and provide essential data for formulation development and stability assessment in accordance with ICH guidelines

This study focused on the formulation and evaluation of oral thin films (OTFs) containing Esomeprazole, a proton pump inhibitor, and Domperidone, a dopamine antagonist, for the management of gastrointestinal disorders. OTFs were developed to address limitations of conventional oral dosage forms, particularly for patients with swallowing difficulties, and to improve solubility, bioavailability, and patient compliance. Film-forming agents such as Hypromellose, Carbomer 974, and Polyvinyl Alcohol were employed, and key formulation parameters—mechanical strength, disintegration time, and drug release—were optimized. Physicochemical evaluations included thickness, weight variation, folding endurance, swelling index, drug content uniformity, and in-vitro disintegration and dissolution studies. A 3² full factorial design was used, with Hypromellose and Carbomer 974 concentrations as independent variables. Among the formulations, F3 exhibited optimal properties, with rapid disintegration (12 seconds), uniform drug content, and excellent dissolution profiles for both drugs. The findings highlight that OTFs offer a promising platform for delivering Esomeprazole and Domperidone, enabling precise dosing, rapid onset of action, and improved therapeutic efficacy, especially for pediatric and geriatric patients. This approach presents a viable alternative to conventional dosage forms in gastrointestinal therapy

No abstract available

Oral route is considered as one of the most convenient route for administration of various pharmaceutical dosage form like tablet, capsule, syrup, suspension and emulsion. Fast Dissolving Drug Delivery systems have developed various fast disintegrating preparations like Oral disintegrating film, ODF. Oral disintegrating film is the solid oral drug delivery system, in which water soluble polymer involve to disintegrate film into mouth fastly. Oral disintegrating film is superior as compare to orally disintegrating tablet as the cost of production is low. The present research was undertaken to develop oral disintegrating film of tteneligliptin hydrobromide hydrate to have rapid onset of action. of tteneligliptin hydrobromide hydrate which is an anti-diabetic. The mechanism action of Teneligliptin is to increase incretin levels (GLP-1 and GIP), which inhibit glucagon release, which in turn increases insulin secretion, decreases gastric emptying, and decreases blood glucose levels.The concept of formulating fast disintegrating film Teneligliptin containing offers a suitable and practical approach in serving desired objective of faster disintegration and dissolution characteristics with increased bioavailability. ODF of Teneligliptin were prepared by solvent casting method and evaluated physicochemical parameters like thickness, weight variation, moisture content, folding endurance, drug content, etc. All the formulations of Teneligliptin ODF displayed optimum folding endurance, which indicates the formulation prepared can withstand handling and transportation. From the results obtained, it was concluded that the formulation of oral disintegrating film has better physical chemical properties with good disintegration property.

Purpose Due to impairments in memory and judgment, it is difficult for dementia patients to understand why they need medicine. Moreover, they often have swallowing difficulties. In this investigation, an oral dissolving film of rivastigmine tartrate (RT-ODF) was developed, offering a unique and convenient formulation for dementia patients. Methods RT-ODF was developed using a solvent-casting technique. Sodium alginate and sodium carboxymethyl cellulose were used as film-forming polymers, and glycerol was used as a plasticizer. A full factorial design (3^2) was employed to estimate the impact of two factors at three levels: polymer concentration (1, 1.5, and 2% w / v ) and plasticizer concentration (30, 40, and 50% w / v ) on the responses, i.e., the tensile strength (TS), the disintegration time (DT), and the quantity of drug released (Q10 min). Results The optimized formula (A1) that had the highest desirability value (0.923) exhibited the lowest tensile strength (3.67 ± 0.72 MPa), the shortest disintegration time (20 ± 2.0 s), and the highest percentage of drug released after 10 min (97.12 ± 2.01%). It was composed of 1% w / v sodium alginate (ALG-Na) and plasticized with 30% w / v glycerol. The pharmacokinetic study revealed that the RT-ODFs enhanced the drug’s bioavailability by 1.91-fold relative to the reference product (Exelon® capsule). Conclusion Oral dissolving films of rivastigmine tartrate could be a promising approach to promote drug bioavailability and convenience for geriatric patients.

The present study aimed to optimize a mouth‐dissolving film (MDF) made from Pongamia pinnata stem bark extract to increase patient compliance and accelerate oral disease therapy. Several stem bark extracts were prepared, and karanjin was used as an herbal marker for the extracts. The ethanolic extract showed the maximum yield (12.10% ± 0.09%) and cytotoxic activity against human oral cancer (KB 3‐1) and embryonic kidney cell lines. The MDF formulation was focused on incorporating a fixed amount of the extract and varying concentrations of HPMC E5 polymer, along with evaluating the performance of plasticizers like PEG 400 and propylene glycol (PG). An optimized formulation was determined based on disintegration time, wetting time, and folding endurance. The formulation consisted of HPMC E5 as a film‐forming polymer, PG as a superior plasticizer, ascorbic acid as an antioxidant, and other ingredients contributing to solubility, dispersion, sweetening, and appearance. High‐performance thin‐layer chromatography‐mass spectrometry analysis confirmed higher levels of karanjin in the optimized formulation, ensuring its successful incorporation and stability. Taste masking evaluations indicate a favorable taste profile and a high potential for patient compliance. The stability study displayed no significant changes in the physical characteristics of the film, affirming its stability and quality. In conclusion, the developed herbal‐based optimized MDF presents a promising drug delivery system, offering enhanced patient compliance, taste masking, and stability. The MDF holds great potential for effective treatment and management of oral diseases, providing convenience and improved therapeutic outcomes.

Subcutaneous injection still dominates insulin and glucagon-like peptide-1 receptor agonist (GLP-1RA) therapy, and honestly, it shows: needle-related pain, lipodystrophy, and non-adherence continue to blunt the real-world benefit of otherwise excellent molecules. This review asks a fairly simple question with a stubbornly complicated answer — can these biologics be swallowed instead of injected, and if so, how close are we? We synthesized recent formulation, device, and clinical literature (2023-2026) describing oral and transmucosal delivery of insulin and GLP-1RAs. Across the gastrointestinal tract, peptides confront a near-continuous gauntlet: gastric acid and pepsin, pancreatic and brush-border proteases, a viscoelastic mucus mesh, tight-junction-sealed epithelium, and, for whatever survives, hepatic first-pass extraction — together limiting unformulated bioavailability to well under 1%. Four broad engineering responses have emerged. Chemical permeation enhancers such as salcaprozate sodium (SNAC) and ionic liquids transiently fluidize membranes, underpinning the only currently approved product, oral semaglutide (Rybelsus®), though its bioavailability remains near 1% and its chronic gut-microbiota effects warrant continued scrutiny. Lipid, polymeric, zwitterionic, and transporter-targeted nanocarriers push relative bioavailability toward the 4-27% range in preclinical models. Ingestible micro-injectors (SOMA, LUMI), buccal and sublingual films, and engineered probiotic secretory depots bypass the gut lumen almost entirely. Meanwhile, non-peptide small-molecule GLP-1RAs sidestep the degradation problem altogether, reaching 20-30% oral bioavailability without enhancers. Taken together, the field has moved from proof-of-concept toward genuinely translatable platforms, though variable inter-subject absorption, excipient safety, and manufacturing scalability remain open questions. We argue that no single strategy is likely to “win” outright; rather, combinatorial and indication-specific approaches will probably define the next generation of non-invasive diabetes biologics.

BACKGROUND Oral dissolving films are portable dosage forms that consist of active pharmaceutical ingredients incorporated into film-forming polymers such as starch. Starches obtain optimum filmogenic properties by gelatinization and blending with other polymers. The high starch content of bitter yam (Dioscorea dumetorum Pax) gives it yet unexplored potential for orodispersible films. OBJECTIVES This study aimed to investigate the effect of pregelatinization on the physicochemical properties of bitter yam starch. Additionally, our objective was to evaluate the potential of both native starch (NS) and pregelatinized starch (PS), incorporated into polymer blends, as biopolymeric materials for use in orally dissolving films (ODFs). MATERIAL AND METHODS Native and pregelatinized wild Dioscorea dumetorum Pax (bitter yam) starch were prepared and characterized using physicochemical, microscopic and rheological methods, Fourier-transform infrared spectroscopy, X-ray diffractometry (XRD), and differential scanning calorimetry (DSC). Oral dissolving films with varying hydroxylpropylmethyl cellulose (HPMC)-to-starch ratios (1:1, 1:2 and 2:1) were formulated and evaluated based on organoleptic properties, surface morphology, folding endurance, weight and thickness, pH, and disintegration time. RESULTS Pregelatinization improved the swelling, solubility and hydration capacity of the starch. Although no changes were observed in the crystalline nature upon gelatinization, DSC analysis revealed remarkable changes in the thermal behavior of the NS after pregelatinization. Both NS and PS did not produce continuous films without HPMC. Flexibility of the starch increased with increasing HPMC concentration films, and PS-based films had higher folding endurance compared to NS films. Native starch-based films had smoother surfaces and higher thicknesses than PS films. All the starch films demonstrated disintegration times longer than 15 min, and slightly acidic pH values. CONCLUSIONS Pregelatinization of bitter yam starch, followed by blending with HPMC at a 2:1 ratio, resulted in the most effective oral film formulation. Further studies focusing on optimizing disintegration rates and pH would help confirm the suitability of this starch for use in ODF formulations.

Clindamycin hydrochloride is a broad-spectrum antibacterial drug belonging to BCS Class 1, characterized by high solubility and rapid absorption. However, conventional oral administration of clindamycin is associated with adverse gastrointestinal effects such as pseudomembranous colitis, nausea, vomiting, and diarrhoea, largely due to disruption of flora. Intravenous or intramuscular administration can further lead to azotaemia, anaphylactic shock, abscess formation and local irritation, which limit patient compliance. To minimize the systemic side effects and improve patient compliance, oral fast dissolving films (OFDF) were developed as an alternative drug delivery system, offering rapid disintegration, faster absorption, and avoiding gastrointestinal irritation. Clindamycin Hydrochloride was formulated using Quality by Design (QbD) principles and optimized with Custom Design, incorporating pullulan – carrageenan polymer blends and optimizing key parameters such as folding endurance, disintegration time, drug content, drug release. The optimized formulation demonstrated – 93.1% in vitro drug release, 92.6% drug content, folding endurance (258) and disintegration time (44seconds) – all within QTPP specifications. The optimized OFDF demonstrated consistent, robust performance, fulfilling the predefined quality criteria.

Injectable peptides such as insulin, glucagon-like peptide 1 (GLP-1), and their agonists are being increasingly used for the treatment of diabetes. Currently, the most common route of administration is injection, which is linked to patient discomfort as well as being subjected to refrigerated storage and the requirement for efficient supply chain logistics. Buccal and sublingual routes are recognized as valid alternatives due to their high accessibility and easy administration. However, there can be several challenges, such as peptide selection, drug encapsulation, and delivery system design, which are linked to the enhancement of drug efficacy and efficiency. By using hydrophobic polymers that do not dissolve in saliva, and by using neutral or positively charged nanoparticles that show better adhesion to the negative charges generated by the sialic acid in the mucus, researchers have attempted to improve drug efficiency and efficacy in buccal delivery. Furthermore, unidirectional films and tablets seem to show the highest bioavailability as compared to sprays and other buccal delivery vehicles. This advantageous attribute can be attributed to their capability to mitigate the impact of saliva and inadvertent gastrointestinal enzymatic digestion, thereby minimizing drug loss. This is especially pertinent as these formulations ensure a more directed drug delivery trajectory, leading to heightened therapeutic outcomes. This communication describes the current state of the art with respect to the creation of nanoparticles containing peptides such as insulin, glucagon-like peptide 1 (GLP-1), and their agonists, and theorizes the production of mucoadhesive unidirectional release buccal tablets or films. Such an approach is more patient-friendly and can improve the lives of millions of diabetics around the world; in addition, these shelf-stable formulations ena a more environmentally friendly and sustainable supply chain network.

The development of oral dissolving film (ODF) of atenolol is an attempt to enhance convenience and compliance for geriatric patients suffering from hypertension. Film former is the most essential component in ODF that determines the physical characteristic and drug release. In this study, three different types of film former including HPMC E5 4% (w/v), 5% (w/v), CMC-Na 3% (w/v), 4% (w/v), and Na-alginate 2.5% (w/v), 3% (w/v) were optimized in Formula 1 (F1) to Formula 6 (F6), respectively. A solvent casting method was employed to develop ODF of atenolol. The films formed by HPMC E5 produced a smooth and flexible surface, whereas CMC-Na and Na-alginate produced gritty textured films. Satisfactory results were obtained from several physical parameters such as film thickness, folding endurance, swelling index, and disintegration time. The homogeneity, drug content, and dissolution properties of ODF with HPMC exhibited better characteristics than the other formulas. Formula 1 exhibited the highest drug release compared to the other ODFs. The molecular docking results showed that there was a hydrogen bonding between atenolol and film formers which was also supported by the FTIR spectrum. The findings of this study suggest that HPMC E5 is the most favorable film former for ODF of atenolol.

Halitosis disebabkan terutama oleh pembusukan bakteri dan generasi senyawa belerang yang mudah menguap. Halitosis memiliki penyebab oral, seperti kebersihan yang buruk mulut, penyakit periodontal, mantel lidah, impaksi makanan, gigi palsu, restorasi yang rusak, karsinoma mulut, dan infeksi tenggorokan. Daun sirih hijau bermanfaat untuk Kesehatan mulut. Daun sirih mengandung senyawa flavonoid, polifenol, tanin dan minyak atsiri . Daun sirih mengandung minyak atsiri sebesar 1 – 4,2%, senyawa fenol dan kavikol. Kavikol yang memiliki aktivitas sebagai bakterisida lima kali lebih kuat dibandingkan dengan fenol. Ekstrak ini dapat berpotensi untuk dijadikan sebagai komponen bahan aktif dalam sediaan orally dissolving film (ODF). Tujuan dari penelitian yaitu untuk mengatahui nilai konsentrasi optimal bahan HPMC sebagai polimer dan propilen glikol sebagai plastisizer berdasarkan sifat fisik seperti pH, keseragaman bobot, ketebalan film, waktu melarut dan uji taste masking dari sediaan orally dissolving film (ODF) ekstrak daun sirih hijau (Piper betle l.). Metode yang digunakan Simplex Lattice Design (SLD) dengan komposisi HPMC sebesar 2% dan propilenglikol sebesar 5%. Hasil respon dari percobaan uji pH dan waktu melarut dengan rata-rata standar deviasi berturut-turut, berkisar 6,67±0,020-6,73±0,026; 122,21± 0,33 -122,85± 0,29 mg; 0,2± 0,005 mm – 0,21± 0,01 mm, dan 20,5± 0,06 - 30,1± 0,05 detik. Pada taste masking memiliki kemampuan cukup baik dalam menutup rasa pahit ekstrak daun sirih hijau.

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Objective: The present work aims to formulate candesartan cilexetil (CC) as nanoparticles oral film to enhance solubility of CC, and promote its dissolution rate, and this could produce rapid therapeutic action of drug. Methods: The nanoparticles prepared by solvent/antisolvent precipitated method then formulated as fast dissolving oral films by casting method.CC nanoparticles formulated by different polymer: drug ratio which was 1:1 and 2:1 hydroxypropyl methylcellulose (HPMC), and polyvinylpyrrolidone (PVP) with different molecular weight like, HPMCE5, HPMCE50, PVPK15 and PVPK30. The effect of polymer type, polymer ratio and injected volume on the size and specific surface area of prepared particle were tested. Results: The bested formula FCC3 was found with a smallest size equal to 37 nm and specific surface area of 54.66m2/g. The FCC3 formula was dried by freeze drier and tested by field emission scanning electron microscope (FESEM), differential scanning calorimetry (DSC) and X-ray powder diffraction analysis (XRD) to determine surface morphology, crystallinity and compatibility, then formulated as fast dissolving oral film. The drug content in the 4 cm2 prepared film was distributed between 93.00% ± 1.75 to 98.25% ± 1.25 and disintegrate in 25min. The in vitro release of candesartan nanoparticle from oral film was 68% in 2 minute and complete to 100% at 4 minutes. Conclusion: The results confirmed fast release and better dissolution rate of prepared candesartan nanoparticle than pure drug.

Buccal delivery offers a promising alternative to oral drug administration by enabling direct systemic absorption and avoiding first-pass metabolism. Multilayer polymeric films represent a promising strategy for the sequential delivery of drug and absorption enhancer in the oral cavity. Here, dual- and triple-layer films were fabricated via slot-die coating, incorporating a GLP-1 receptor agonist (GLP-1-RA) and the penetration enhancer sodium glycodeoxycholate (GDC). These were co-loaded in dual-layer films or compartmentalized in triple-layer films. Scanning electron microscopy and optical coherence tomography confirmed well-defined, distinct layers with thicknesses suitable for buccal administration (339 ± 10.24 µm and 487 ± 36.5 µm for dual- and triple-layer films, respectively). Both designs exhibited good mucoadhesion and mucosal compatibility, and preserved the secondary structure of GLP-1-RA. In vitro release studies showed rapid diffusion of GDC and GLP-1-RA from dual-layer films, whereas triple-layer films enabled sustained, sequential release of GDC and GLP-1-RA. Ex vivo porcine buccal mucosa studies showed higher GLP-1-RA and GDC flux from triple-layer films compared to dual-layer films. The films also did not compromise epithelial integrity, in contrast to the direct application of GLP-1-RA and GDC, which caused significant epithelial disruption. These results demonstrate that multilayer film architecture and spatial layering can be harnessed to control release kinetics, maximize peptide penetration, and minimize tissue stress, offering a versatile platform for safe and effective peptide delivery. Graphical abstract

The goal of this study was to improve Melatonin's oral bioavailability and give a faster onset of action by creating an oral fast dissolving film. Melatonin has a low aqueous solubility, and due to first-pass metabolism, its oral bioavailability is only about 33%. Melatonin oral rapid dissolving film was made by solvent casting with HPMC-E5 (film forming polymer), PEG-400 (plasticizer), -cyclodextrin (solubilizing agent), citric acid (saliva stimulating agent), and mannitol (sweetening agent). For the formulation optimization of oral fast dissolving film of Melatonin, a two factor three level factorial design (32) was used, with experimental trials performed on all possible formulations, in which the amount of HPMC-E5 (X1) and amount of PEG-400 (X2) were selected as independent variables (factor) and varied at three different levels: low (-1), medium (0), and high (+1) levels. The dependent variables were percent medication release and disintegration time (response). The thickness, weight variation, folding endurance, weight variation, surface pH, drug content, disintegration time, and in-vitro drug release of each formulation were all assessed. According to the findings, oral fast dissolving film (F6) avoids first pass metabolism, improves oral bioavailability, and has a quick onset of action.

The primary objective of the present research work was to develop nanoparticles incorporating (nanoparticulate) fast dissolving (orodispersible) film evincing enhanced solubility and bioavailability of nitrendipine (NIT). An antisolvent sonoprecipitation method was employed to produce the NIT nanosuspension (NS), which was optimized using the 32 optimal response surface design and then the optimized one was evaluated for various parameters (Gandhiet al., AAPS PharmSciTech 22 (1):1–15, 2021). The NIT nanoparticulate orodispersible film (N-ODF) was prepared utilizing the nanosuspension by the solvent casting method using the Vijay film-forming instrument. The N-ODF was optimized by the 23 full factorial design and was evaluated for several parameters. The optimized NS depicted a particle size of 505.74 ± 15.48 nm with a polydispersity index (PDI) of 0.083 ± 0.006 (Fig. 1b). The NIT nanoparticles showed a striking increment in saturation solubility (26.14 times), when compared with plain NIT (2). The developed NIT N-ODF exhibited thickness (0.148 ± 0.008 mm), folding endurance (280.33 ± 5.51 times), surface pH (6.86 ± 0.05), tensile strength (8.25 ± 0.13 kg/cm2), % elongation (63.5 ± 1.97%), and disintegration time (24.60 ± 1.31 s) to be within the standard intended limit. The in vitro dissolution study unveiled 100.28 ± 2.64% and 100.68 ± 2.50% of NIT release from lyophilized nanocrystals (in 8 min) and N-ODF (in 3.5 min), respectively, whereas the conventional NIT tablet took 30 min to release 99.94 ± 1.57% of NIT (Gandhi et al., AAPS PharmSciTech 22 (1):1–15, 2021). The in vivo pharmacokinetic study in rabbits inferred the achievement of significantly (p < 0.05) higher bioavailability of NIT on release from N-ODF in comparison to the conventional NIT tablet. Thus, the generation of N-ODF can be considered as a propitious move toward improving the efficacy of NIT to treat hypertension and angina pectoris.

Oral thrush and throat infections can occur in a wide range of patients. Treatments are available; however, resistance to drugs is a major problem for treating oral and throat infections. Three-dimensional printing (3DP) of fast dissolving oral films (FDFs) of linalool oil may provide an alternative solution. Linalool oil FDFs were printed by fused deposition modelling across 1-18% w/w linalool content range with nozzle diameters of 0.4 or 1 mm at the temperature range of 150°C-185°C. The FDFs were evaluated for physicochemical and mechanical properties. Increasing the printer nozzle diameter to 1 mm allowed reducing the printing temperature from 185°C to 150°C; consequently, more linalool was quantified in the films with improved content uniformity. The higher linalool content in the films increased the film disintegration time and mechanical strength. FDFs containing 10% w/w linalool showed clear antifungal activity against Candida albicans. Raman spectroscopy suggested linalool separation from excipients at higher temperature printing. Viscoelastic measurements indicated that to achieve printing; the elastic modulus of molten filament needed to be higher than the loss modulus at low angular frequencies. In conclusion, increasing the printing nozzle diameter may avoid loss of the active ingredient by reducing the temperature of the 3DP process.

Aim: This study aimed to develop a mouth dissolving film of Ondansetron HCl. Materials and Methods: Solvent casting method is used, and various film forming polymers such as dried cassia tora gum, konjac gum, and PVP K30 in various concentrations were evaluated. The effect of independent factors, such as dried cassia tora gum, konjac gum, and PVP K 30 concentrations, on two dependent variables, such as disintegration time and percentage drug content, was examined using the 33 factorial design. The optimized formulation was identified based on a disintegration time of 5–30 s and a drug release exceeding 85%. Batches F5, F8, F-14, F20, F24, and F25 of the formulation show promising results. Results: As a result, each of these formulation batches were considered as optimized formulations and processes for in vitro dissolution testing. Batch F25 has a rapid disintegration time of 18.50 s and also the % drug release of 96.10% within 120 s. It contains 1% cassia tora gum, 1% konjac gum, and 1% PVP K30. Conclusion: From the results of this study, it can be interpreted that mouth-dissolving films of Ondansetron hydrochloride are feasible to prepare, provide quick onset of action, and have improved oral bioavailability using natural polymers.

Background and objective: Fast-dissolving oral thin film (FDOF) is a novel and most advanced form of solid dosage form that dissolves or disintegrates in 1 minute when put in the mouth without water or chewing. Pre-gastric absorption of FODFs from the mouth, pharynx, and esophagus as saliva flows down into the stomach would improve the therapeutic benefit of the drug as oral films disintegrated in the mouth. The study is designed and purposed to use most water soluble, best type and concentration of polymers to be selected for use in combination to formulate melatonin oral thin films. Different types of synthetic water soluble polymers were utilized the preparation of films (hydroxypropyl methyl cellulose HPMC15M, sodium carboxy methyl cellulose NACMC). Methods: Solvent casting method was performed for preparation of twelve placebo films at the beginning, to obtain and select suitable polymer type and concentration for use in combination to be formulated for drug loading. The films were evaluated for their characteristics like mechanical properties (thickness and folding endurance), surface pH and disintegration time. Percentage of release and assay of melatonin was taken. Comparison studies were performed on melatonin films from this study with melatonin oral disintegrating tablets release profiles. Best batch could be selected. Drug-excipient compatibility carried out as pre formulation study to see whether there is interaction between the drug and excipients used. Results: Results from FT-IR showed no interaction between melatonin and polymers used, the prepared formulations were clear, transparent, non-sticky and easily removed from the plate surface with the thickness ranging from (0.04-0.07) mm depending on the polymer concentration. The times required for the films to disintegrate was ranging from 21-26 seconds, and the majority of melatonin was released within first 2 minutes within the dosage form. Conclusion: Melatonin can be formulated as fast dissolving oral films using combination of water-soluble polymers by solvent casting method to obtain ease of administration without using water during administration, fast onset of action resulted from rapid disintegration.

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No abstract available

The first-pass effect and low water solubility are crucial limitations that hinder the drug from being absorbed into the systemic circulation, followed by oral administration. The mucoadhesive buccal delivery system offers direct drug absorption through the mucosa, reaching systemic circulation and bypassing the hepatic first-pass metabolism. This approach ensures high bioavailability and overcomes the swallowing difficulties associated with traditional oral delivery systems. Here, we developed mucoadhesive buccal films for oral delivery of poorly water-soluble drugs using hot-melt extrusion (HME). Poly(2-ethyl-2-oxazoline) (PEtOx), a potential pharmaceutical excipient with high biocompatibility and versatility, was used as the primary matrix for solubility enhancement. Fenofibrate (FB), a typical Biopharmaceutics Classification System (BCS) class II drug with virtually insolubility in water, was used as the model drug. Hydroxypropyl cellulose (HPC), hydroxypropyl methylcellulose (HPMC), and polyethylene oxide (PEO) were combined with PEtOx to adjust the mucoadhesive property. The prepared films were in vitro characterized to delineate the impact of key formulation factors on the mechanical properties, bioadhesion, and solubility enhancement effect. We demonstrated that the complexation of PEtOx with 20% PEO (F8) resulted in over 95% drug release within 2 h, representing an over 5-fold enhancement in solubility compared to the free drug. This F8 formulation exhibited significant bioadhesion among the other formulations, with a 2.2- to 2.7-fold increase in Peak Force (PAF) and work of adhesion (WAD) relative to the control group. This study investigates HME as a continuous fabrication process for developing PEtOx-based buccal film, demonstrating a potential bioadhesive drug delivery system with a solubility improvement effect.

No abstract available

: Vortioxetine hydrobromide is an atypical antidepressant used in the treatment of major depressive disorder (MDD). However, its oral bioavailability is limited due to poor solubility and first-pass metabolism. To address these challenges, a buccal film formulation of vortioxetine hydrobromide was developed. Buccal films offer a convenient, patient-friendly alternative to oral tablets, providing improved bioavailability due to direct absorption through the buccal mucosa. The formulation was designed to enhance drug release, optimize the physicochemical properties, and ensure stability. This research focuses on the formulation, evaluation, and potential therapeutic benefits of buccal films for vortioxetine hydrobromide.

This study explores the development of buccal films as an innovative drug delivery system for hypertension management, combining candesartan cilexetil (CC) and hydrochlorothiazide (HCTZ). Utilizing a solvent casting technique, films were prepared with various polymers, including PVA, PVP, and CMC Na, and enhanced with plasticizers to improve solubility and bioavailability. The films were evaluated for physicochemical and mechanical properties, disintegration time, and drug content uniformity. Results demonstrated that the films were visually uniform, with excellent folding endurance and a neutral pH. The formulation containing PVA, PVP, and CMC Na exhibited the fastest disintegration rate and superior bioadhesion. The use of Dynamic Mechanical Thermal Analysis (DMTA) confirmed the miscibility of the drugs within the polymeric matrix, ensuring effective delivery. This novel formulation offers significant advantages by improving patient compliance and bypassing first-pass metabolism, presenting a promising alternative for hypertension treatment.

A buccal film is a thin film of medication placed between the gum and cheek and left to dissolve. It is commonly used as a method of drug delivery, particularly for medications that need to be administered in small doses over a long period of time. The film typically contains active pharmaceutical ingredients in a variety of forms, including powders, granules, or gels. It is typically placed with a device, such as a spatula, and it dissolves rapidly and completely after being placed in the mouth. The benefits of buccal films include convenience, compliance, improved patient outcomes, and better patient satisfaction. The main disadvantage is that the dosage may not be as accurate as with other drug delivery methods. Buccal films is that they are an effective and safe method of administering medication to patients. Buccal films offer a fast and easy method of delivering drugs, with minimal risk of side effects, making them a preferred method of drug delivery for many patients and healthcare professionals.

Background Buccal drug delivery is a novel drug delivery system ensure fast onset of action and avoids the first pass metabolism and ultimately improves the bioavailability. Aim The present investigation is oriented towards design and development of Fast Dissolving Buccal Film (FDBF) of Ivabradine HCl (BCS Class I drug) by applying Quality by Design (QbD) concept. Materials and Methods The Quality Target Product Profile was defined for the proposed formulation, CQA’s were identified and risk assessment was carried to identify the most critical factors associated with the formulation development. Main Effect Screening design was applied by using independent variable as HPMC and Kopulan-PG, PEG 400, Tween 80 as material attributes that have an impact on responses such as Folding endurance, Disintegration time, % Drug content and % Drug release at 15 min. The stability data obtained for the optimal formulation was computed in the JMP stability toolbox to predict the expiration date. Results The results of the main effect screening design of 12 formulations indicated that the combined action of three factors had a significant impact on Ivabradine release and could predict the ideal formulation with the necessary Quality target product profile (QTPP). The statistically significant models were determined for % drug release at 15 min (R2=0.97) disintegration time (R2=0.99), folding endurance (R2=0.99) and drug Content (%) (R2=0.98). The optimal formulation confirms the expiration date of 25 months. Conclusion The selected factors and responses have a strong association and are significant enough for formulation optimization, because the highest global desirability value obtained was 0.80.

Chlorthalidone is a thiazide-like diuretic drug used in the treatment of hypertension. It belongs to class IV of Biopharmaceutical Classification System (BCS) and exhibits first pass metabolism leading to low bioavailability. The present work was undertaken to formulate mucoadhesive buccal film of chlorthalidone with an objective to improve bioavailability, therapeutic efficacy, and patient compliance. Film formulations were prepared by solvent casting method using a combination of different grades of hydrophilic polymer, Hydroxypropyl methylcellulose with suitable plasticizer. Other important excipients used were solubilizing agents to increase solubility and permeation enhancers to increase the permeability of the drug. The developed films were evaluated for physicochemical characteristics such as thickness, content uniformity, surface pH, and in vitro drug release etc. The optimized formulation containing a combination of hydrophilic and hydrophobic polymers showed good tensile strength, mucoadhesive strength and optimum in vitro diffusion results. The Ex vivo Drug permeation through porcine oral mucosa at the end of 8 hours was found to be 87.2±0.93%.

Objective: The aim of this work was to develop and evaluate bucco-adhesive films of Loratadine (LTD) for sustained release use. Methods: Design of twelve different sustained released buccal film formulas using Carbopol, pectin, sodium alginate, glycerol, carboxymethyl cellulose (CMC), hydroxypropyl cellulose (HPC), Gelatin, Hydroxyethyl cellulose (HEC), and Hydroxypropyl methylcellulose (HPMC) as mucoadhesive polymers. Films were evaluated for physicochemical properties, thickness, swelling, moisture content, drug content, in vitro dissolution. The pharmacokinetic parameters of optimal formula were evaluated in beagle dogs. Results: The selected film formula (F6) showed accepted content and muco-adhesion properties. The in vitro release study showed prolonged release of drug from films over 10 h in optimal formulation. The bioavailability studies performed using beagle dogs model showed that there was 113.45% increase in the AUC0-24 of selected film compared with oral market tablets. Conclusion: Bucco-adhesive films is a promising dosage form for improving the bioavailability of loratadine.

Abstract. Diltiazem Hydrochloride (HCl) is commonly used in hypertension therapy for its beneficial effects, such as reducing blood vessel pressure resistance and relaxing the heart muscles. In an in-vivo study, Diltiazem HCl is known to be decrease by 60% of its bioavailability due to first-pass metabolism. Thus, it is necessary to develop a new administration route, some of which is buccal drug delivery route in mucoadhesive buccal film. Moringa gum is a polyuronide polymer with a hydroxyl group in its side chains, giving the potential use as a mucoadhesive polymer. However, it has poor folding endurance and its release kinetics study has not been investigated. Polyvinyl alcohol (PVA) is a water-soluble polymer with hydroxyl side chain. PVA is known for its high tensile strength and flexibility, though it can be affected by humidity. The aim of this research is to determine the right amount of moringa gum and PVA to obtain a film with good physical characteristics and mucoadhesive residence time. In this study, the optimization of moringa gum and PVA was carried out using factorial design. Mucoadhesive buccal film was prepared by solvent casting method, the films were later evaluated and the obtained responses were analyzed by Software Design Expert 11.0.0. The optimization result shows the film containing the amount of moringa gum 2% and PVA 5% can produce the optimum formula. The mucoadhesive buccal film formula has surface pH of 6.083, mucoadhesive residence time of 445.055 min, swelling index of 4.067, and 87.9913% drug release in in-vitro drug release study after 420 min following the Higuchi model release kinetics. Therefore, it can be concluded that the obtained optimum formula of mucoadhesive buccal film can be used in the preparation of mucoadhesive buccal film Diltiazem HCl.. Kata Kunci:  Hypertension; Diltiazem HCl; Mucoadhesive buccal film; Moringa gum; PVA.

The goal of the current study was to formulate and produce a felodipine buccal film that dissolves quickly utilising the solvent casting process. mucoadhesive polymers HPMC E15 and PVP were used to make mucoadhesive buccal films. Because HPMC E15 has a high mucoadhesive characteristic, it demonstrated an extended in-vitro residence period when compared to the other polymer

Buccal film technology has emerged as a promising approach for diabetes management due to its unique advantages over conventional dosage forms. This review paper explores the significance of buccal films in diabetes management, highlighting their benefits, challenges, and potential applications. Additionally, we delve into the biocompatibility and safety considerations associated with buccal films, addressing concerns related to patient acceptability and long-term use. The review emphasizes the need for further research and development to fully harness the potential of buccal films in revolutionizing diabetes treatment. Type 2 diabetes mellitus (T2DM) is a prevalent metabolic disorder characterized by insulin resistance and impaired glucose regulation. The conventional oral antidiabetic medications for T2DM have limitations such as poor patient compliance, gastrointestinal side effects, and hepatic first-pass metabolism. Buccal film formulations have emerged as a promising alternative for the improved management of T2DM, offering direct drug absorption through the buccal mucosa, bypassing the gastrointestinal tract and hepatic metabolism. This review paper aims to discuss the development and evaluation of buccal film formulations for the effective and convenient treatment of T2DM, focusing on formulation strategies, drug candidates, evaluation techniques, patient compliance, and future perspectives.

Buccal films has distinct advantages over conventional dosage forms. Drugs can be delivered through buccal route, by avoiding first pass metabolism to produce local and systemic action. Rapid absorption of the drug is achieved because buccal mucosa is highly permeable with rich blood supply. Only few dosage forms are designed to deliver the drug through this route. Leaf extract of Mimosa pudica has number of pharmacological actions. Buccal film of leaf extract of mimosa pudica is prepared by solvent casting method and evaluated for its characteristics. Six formulations were prepared, out of which F3 formulation was found promising formulation, releases 96.13% of drug in 10 minutes.

Cannabidiol is a non-psychoactive cannabinoid isolated from the cannabis plant. Instead of intoxicating effects, Cannabidiol is known for its antioxidant, anti-inflammatory, and anti-anxiety effects. Being antagonist to cannabinoid receptor type 1 (CB1) and cannabinoid receptor type 2 (CB2) cannabinoid receptors, Cannabidiol binds to CB receptors through negative allosteric modulation; reduce binding affinity of endocannabinoids to corresponding receptors decreasing activities without adverse agonist effects. Cannabidiol could be administered via several routes, for example, oral, sublingual, nebulizing, and transdermal. However, due to its low water solubility and first-pass metabolism, Cannabidiol showed low bioavailability in several administrations, including the most common, oral delivery. Mucoadhesive drug delivery is one solution to increase drug retention time at oral absorption sites, buccal and sublingual, in which the drug could be absorbed directly into the bloodstream without passing through the digestive tract and its first-pass metabolism. Among several biocompatible mucoadhesive polymers, hydroxypropyl methylcellulose (HPMC) was found to be a suitable matrix that could be formulated into a thin film with up to 20% cannabidiol (CBD) content. To prolong the retention and disintegration time, polyvinyl alcohol (PVA) was added as a backing layer due to its softness and flexibility. The bilayer film showed excellent mechanical properties with tensile strength of 8.54 N/mm^2 and elongation of 30%. The addition of a PVA backing layer not only improves mechanical properties but also prolongs up to 90 min of film disintegration time. HPMC-PVA film shows the controlled release of cannabidiol over a 4-hour period. The results indicate that HPMC-PVA bilayer is a suitable polymer matrix for cannabidiol delivery because it provides mucoadhesive properties in oral administration and controls release for higher cannabidiol absorption. Graphical Abstract

Abstract Introduction Cannabidiol (CBD) has sparked considerable interest because of its wide range of pharmacological uses and the fact that it does not induce psychoactive effects. CBD formulation development presents significant challenges due to its limited water solubility and susceptibility to first-pass metabolism, both of which restrict its overall bioavailability. The current research aimed to use hot-melt extrusion (HME) technology to develop mucoadhesive buccal films to improve CBD solubility and reduce first-pass metabolism. Methods Five formulations containing 10% w/w CBD were extruded using a counter-rotating twin-screw extruder (Haake Minilab II, Thermo Fisher Scientific). Different characterization studies were conducted on the developed formulations. Results Differential scanning calorimetry (DSC) revealed that the CBD endothermic peak disappeared in some of the developed films, indicating that CBD was converted from crystalline to amorphous form. A bio-adhesion study showed that the formulations containing Carbopol® (BF2, BF3, BF4, and BF5) had higher adhesiveness properties. In vitro release and solubility studies showed an increase in CBD release and water solubility in the developed formulations when compared to pure CBD. Stability studies revealed that CBD content and release in the lead formulation (BF2) was stable over 15 months. Conclusion The current study demonstrates that HME was successfully used as an approach to develop CBD mucoadhesive buccal films and CBD solubility was enhanced.

Drug solubility and dissolution remain a significant challenge in pharmaceutical formulations. This study aimed to formulate and evaluate repanglinide (RPG) nanosuspension-based buccal fast-dissolving films (BDFs) for dissolution enhancement. RPG nanosuspension was prepared by the antisolvent-precipitation method using multiple hydrophilic polymers, including soluplus®, polyvinyl alcohol, polyvinyl pyrrolidine, poloxamers, and hydroxyl propyl methyl cellulose. The nanosuspension was then directly loaded into BDFs using the solvent casting technique. Twelve formulas were prepared with a particle size range of 81.6–1389 nm and PDI 0.002–1 for the different polymers. Nanosuspensions prepared with soluplus showed a favored mean particle size of 82.6 ± 3.2 nm. The particles were spherical and non-aggregating, as demonstrated by SEM imaging. FTIR showed no interaction between soluplus and RPG. Faster dissolution occurred for the nanosuspension in comparison with pure RPG (complete release vs 60% within 30 min). The nanosuspension was successfully incorporated into BDFs. The optimum film formula showed 28 s disintegration time, and 97.3% RPG released within 10 min. Ex-vivo permeation profiles revealed improved RPG nanosuspension permeation with the cumulative amount of RPG permeated is103.4% ± 10.1 and a flux of 0.00275 mg/cm2/min compared to 39.3% ± 9.57 and a flux of 0.001058 mg/cm2/min for pure RPG. RPG was successfully formulated into nanosuspension that boosted drug dissolution and permeation. The selection of the ultimate NP formula was driven by optimal particle size, distribution, and drug content. Soluplus NPs were shown to be the successful formulations, which were further incorporated into a buccal film. The film was evaluated for ex-vivo permeation, confirming successful RPG formulation with improved performance compared to pure drugs.

This research aimed to develop mucoadhesive buccal films incorporating nanostructured lipid carriers (NLCs) loaded with triamcinolone acetonide (TN-films). A Box–Behnken design was employed as a systematic approach to optimize the formulation. Key components of the NLCs—spermaceti, soybean oil, and polysorbate 80—were considered independent variables. The NLCs were prepared and size-reduced using a combination of hot homogenization and ultrasonic probe techniques. Films were cast using hydroxypropyl methylcellulose (HPMC) as the film-forming agent. The TN-films were characterized based on weight, thickness, tensile strength, elongation at break, contact angle, and surface free energy. Linear regression showed that spermaceti increased film weight and thickness, while polysorbate 80 decreased them. The mechanical strength of the films was primarily influenced by spermaceti; higher concentrations of spermaceti resulted in decreased film strength. Additionally, all independent variables contributed positively to the lipophilicity of the films. The TN-films were found to sustain drug release via a Fickian diffusion mechanism, exhibiting rapid swelling and favorable mucoadhesive properties. Moreover, the TN-films demonstrated superior drug release and permeation to pastes and films loaded with emulsions. These findings suggest that the TN-films represent a promising and effective approach for the buccal delivery of triamcinolone acetonide.

Therapeutic proteins often require needle-based injections, which compromise medication adherence especially for those with chronic diseases. Sublingual administration provides a simple and non-invasive alternative. Herein, two novel peptides (lipid-conjugated protamine and a protamine dimer) were synthesized to enable sublingual delivery of proteins through simple physical mixing with the payloads. It was found that the novel peptides promoted intracellular delivery of proteins via increased pore formation on the cell surface. Results from in vitro models of cell spheroids and human sublingual tissue substitute indicated that the novel peptides enhanced protein penetration through multiple cell layers compared to protamine. The novel peptides were mixed with insulin or semaglutide and sublingually delivered to mice for blood glucose (BG) control. The effects of these sublingual formulations were comparable to the subcutaneous preparations and superior to protamine. In addition to peptide drugs, the novel peptides were shown to enable sublingual absorption of larger proteins with molecular weights from 22 to 150 kDa in mice, including human recombinant growth hormone (rhGH), bovine serum albumin (BSA) and Immunoglobulin G (IgG). The novel peptides given sublingually did not induce any measurable toxicities in mice.

The management of diabetes relies heavily on macromolecular biologics, which are predominantly administered via subcutaneous injection. However, its invasiveness compromises patient compliance and leads to injection-related complications. Among all the clinically attractive alternatives, mucosal administration, while non-invasive and enabling rapid absorption, faces significant challenges from physiological barriers that limit drug permeability. Herein, we engineered a novel choline-salcaprozate ionic liquid (CS-IL) system that could overcome these limitations and enable efficient mucosal delivery of insulin and semaglutide. To evaluate its potential, comprehensive in vitro and in vivo studies were conducted, which revealed that CS-ILs significantly enhanced drug permeability and mucosal retention via both intranasal and sublingual routes, thereby achieving robust hypoglycemic effects comparable to subcutaneous injection. Notably, a key mechanistic insight uncovered that CS-ILs boost paracellular transport via the transient and safe modulation of intercellular junctions. Consequently, with its compelling biocompatibility profile and potent efficacy across mucosal routes, this versatile IL platform emerges as a promising strategy for clinical translation, potentially revolutionizing non-invasive delivery for diabetes therapeutics.

No abstract available

In this review, our intention was to shed some light on the history of sublingual and buccal delivery over the past 75 years. By searching the query sublingual and buccal, we noticed four steady growth periods in the number of publications between 1950 and 2025. The early phase of sublingual and buccal drug delivery (1950–1982) saw limited attempts to explore this delivery route. The exploratory growth phase (1983–1993) was marked by the use of nitroglycerin to treat angina, calcium channel blockers to treat hypertension, ACE inhibitors to treat heart conditions, the use of opioids in pain management therapy, and peptide and hormonal therapy. The diversification and discovery phase (1994–2009) was marked by the introduction of small molecules for the treatment of opioid use disorder and analgesia, the use of animal models to enhance the pharmacokinetic understanding of the sublingual and buccal route, the use of penetration enhancers, peptide and hormonal therapy, and few marked FDA drug approvals in this area. The innovation and integration phase (2010–2025) was marked by the use of nanoparticles, multilayered mucoadhesive systems, pediatric formulations (fast-dissolving films and tablets), immunotherapy and vaccine delivery, and a broad spectrum of therapeutic agents, such as steroids, antifungals, cannabinoids, antidepressants, antipsychotics, and narcotics (e.g., buprenorphine and apomorphine), novel formulations of fentanyl and diazepam for pain and seizure control, and the introduction of buccal vitamin D3 sprays. Understanding the history of sublingual and buccal delivery demonstrates a growing area of research focused on enhancing mucosal drug delivery for achieving local and systemic therapeutic benefits.

Type-2 diabetes mellitus (T2DM) is a chronic metabolic condition with more than 95% of the cases worldwide and can cause complications like retinopathy, nephropathy, cardiovascular problems, etc. Currently, major treatment protocols available for T2DM include oral hypoglycemic agents, insulin, and GLP-1 receptor agonists. Due to the unique mechanism of action, human glucagon-like peptide-1 (HuGLP-1) has been a focus for management of T2DM. Oral HuGLP-1 delivery is hindered by its hydrophilic nature, preventing intestinal absorption. Additionally, the unfavorable gut environment and hepatic metabolism significantly restrict its bioavailability. Sublingual administration offers a potential solution bypassing these obstacles. This route avoids first-pass metabolism and prevents enzymatic exposure of peptide thus enhancing its absorption. The goal of the present work is to design HuGLP-1 loaded hydrogel embedded with nanoliposomes that would protect it from systemic enzymes and extend the duration it spends in the bloodstream, improving its pharmacological activity. The particle size, polydispersity index, and entrapment efficiency of optimized HuGLP-1-NLs were found to be 179.2 ± 1.65 nm, 0.167 ± 0.01, and 47 ± 2.18%, respectively. Post sublingual delivery of HuGLP-1 NLs loaded hydrogel in T2DM induced SD rats, it showed significantly less reversal of hypoglycemia than the standard hydrogel (p < 0.001). In summary, extended sublingual administration of this formulation could boost T2DM management by improving patient compliance. This formulation could also be used for managing diabetes-related obesity and needs to be validated by preclinical testing on a large number of animal models.

We earlier reported comparable efficacy in bone parameters of sublingually administered salmon calcitonin hydroxyapatite nanoparticles (SCT-HAP-NPs) compared to the subcutaneous injection, in the ovariectomy rat model, despite a bioavailability of barely ~ 15%. We ascribed this intriguing finding to targeted bone delivery, facilitated by translocation of significant quantity of intact NP into systemic circulation. In the present study we track the translocation of FITC-SCT-HAP-NPs (~ 100 nm) across porcine sublingual mucosa using the Franz diffusion cell to validate our hypothesis. Confocal Laser Scanning microscopy (CLSM) established that SCT-HAP-NPs permeated into the deeper layers of sublingual porcine mucosal tissue. We confirmed the nanoparticles were present in the receptor medium of the Franz diffusion cell by DLS and TEM. We also demonstrate for the first time quantification of the NPs (%) translocated across the porcine mucosa, using the Amnis Image StreamX Mk II imaging flow cytometer. Computation revealed transport of ~ 60% of the FITC-SCT-HAP-NPs across mucosa in 2 h, substantiated that high NP concentrations could reach systemic circulation. Such high NP concentration in systemic circulation coupled with the small size (~ 100 nm) and the high bone affinity of HAP, validate our hypothesis of targeted bone delivery following sublingual administration. Furthermore, quantification of translocated NPs, which we demonstrate for the first time, would permit rational development of optimal targeted nanoparticulate carriers for delivery by noninvasive routes.

Drug delivery via the sublingual mucosal route presents considerable challenges due to the presence of a complex mucus barrier. To improve the mucus permeability of resveratrol and bovine serum albumin (BSA) and achieve their co-delivery, muco-inert resveratrol-BSA nanoparticles (Res-BSA) were prepared. The mucus penetration of Res-BSA was 3.6 times higher than that of resveratrol and BSA. Res-BSA was incorporated into sublingual films based on mucoadhesive tamarind seed polysaccharide and pullulan (TSP-Pul) to prolong its residence time in the sublingual area. The introduction of Res-BSA enhanced the surface roughness and hydrophilicity of TSP-Pul and preserved the favorable mechanical strength and flexibility of TSP-Pul. The 5 % addition of Res-BSA dramatically increased the initial swelling capacity (435 % at 2 min) of TSP-Pul (284 % at 2 min), and all films completely disintegrated within 60 min. During disintegration, the holes in the internal network of the films became progressively larger and more heterogeneous. The main initial release form of the films containing Res-BSA was determined to be nanoparticles. Compared to TSP-Pul, the addition of 1 % Res-BSA accelerated the release of resveratrol and BSA within the first 2 h. Overall, TSP-Pul containing Res-BSA may be an attractive platform for sublingual co-delivery of resveratrol and BSA.

Introduction Injectable formulations are common for protein-based therapeutics. However, non-injectable formulations are crucial for improving patient compliance. This study aims to develop hyaluronic acid/aminoclay-based dissolving microneedles as a noninvasive delivery system for semaglutide in the treatment of obesity. Methods The core nanocomplex (Sema-AC) was formed by combining semaglutide (Sema) with aminoclay (AC) via electrostatic interaction. This nanocomplex was then mixed with hyaluronic acid (HA) of varying molecular weights and poured into a reverse polydimethylsiloxane (PDMS) mold to create dissolving microneedles (MNs). Various in vitro and in vivo studies were performed to evaluate the physicochemical properties and therapeutic efficacy of the MNs. Results Among the developed MNs, Sema-AC/HA10 demonstrated a mechanical strength of 0.37 ± 0.020 N/needle and retained stable physicochemical and morphological properties at 25°C during storage. Encapsulated Sema retained its conformational stability within the MNs. Sema-AC/HA10 dissolved rapidly upon skin insertion, enabling efficient transdermal drug absorption. The MNs containing Sema-AC nanocomplex significantly enhanced the systemic drug exposure compared to the MN loaded with the free drug. Consequently, Sema-AC/HA10 demonstrated in vivo efficacy comparable to that of subcutaneous Sema injection in type 2 diabetic rats, significantly reducing blood glucose, HbA1c, total cholesterol, triglycerides, food intake, water consumption, and body weight”. Conclusion These findings suggest that Sema-AC/HA10 is an effective transdermal delivery system for semaglutide.

This study introduces a novel dual-sensitive drug delivery system, gelatin-coated chitosan microparticles (GL-ChMPs), designed to enhance the lung targeting and therapeutic efficacy of semaglutide (SEM). GL-ChMPs were designed to respond to the acidic environment and metalloproteinases, conditions that are typical in pulmonary fibrosis. SEM-GL-ChMPs exhibited superior lung targeting and prolonged retention while minimizing systemic distribution. SEM-GL-ChMPs demonstrated 21-fold and 2-fold higher time-averaged lung drug exposure compared to free SEM solution and uncoated ChMPs, respectively. In a bleomycin-induced chronic lung injury model, SEM-GL-ChMPs effectively attenuated inflammation and fibrotic progression in lung tissues. On the inflammatory front, SEM-GL-ChMPs significantly reduced immune cell infiltration, which was accompanied by lower BALF total protein and LDH, suggesting reduced alveolar-capillary barrier disruption and cellular injury. At the molecular level, there was a marked inhibition of TLR4/NFκB signaling and a downregulation of pro-inflammatory cytokines TNF-α, IL-6, and IL-8. On the fibrotic side, SEM-GL-ChMPs resulted in a pronounced decrease in key fibrogenic mediators, including TGF-β1 and p-SMAD3, and critical markers like α-SMA and Col1a1. Histopathological analysis further reinforced these findings. The gelatin coating was designed to exploit MMP-2 overexpression in fibrotic lungs, enabling localized drug release. Our data confirmed that metalloproteinases are positively correlated with fibrosis progression, supporting the rationale for this enzyme-responsive delivery approach. Collectively, SEM-GL-ChMPs not only improved lung-specific drug delivery and retention but also effectively mitigated the hallmarks of chronic lung injury at cellular, molecular, and tissue levels. This underscores their promise as a precision-targeted, dual-sensitive platform for managing chronic inflammatory and fibrotic lung diseases.

Abstract Both local and systemic medication delivery benefit greatly from the sublingual and buccal modes of administration. They have shown to be a successful substitute for the conventional oral route, particularly in situations requiring a quick commencement of action. Via venous drainage to the superior vena cava, drugs can enter the systemic circulation quickly and directly. They are therefore helpful for individuals who have trouble swallowing as well as for medications that are highly cleared by the liver or degraded in the gastrointestinal system. Traditionally, medications that are delivered through the buccal and sublingual channels are made in three different dose forms: liquid (such as sprays and drops), semi-solid (such as gels), and solid (such as pills, wafers, films, and patches). Physiological variables frequently influence conventional dose forms, which might decrease the formulation’s interaction with the mucosa and result in unexpected medication absorption. Many formulation development advancements have been made to enhance medication absorption and retention in the buccal and sublingual areas. The physiological factors influencing buccal and sublingual drug delivery as well as developments in nanoparticulate drug delivery techniques for sublingual and buccal administration will be the main topics of this review. It also discusses about the clinical development pipeline, which includes formulations that have been authorized and are undergoing clinical studies.

This study aims to compare the single-dose pharmacokinetic profiles of semaglutide administered via sublingual, oral, and injectable routes in Sprague-Dawley rats. Semaglutide was delivered sublingually in a proprietary anhydrous suspension vehicle. Rats were randomized into five groups and received the following treatments: subcutaneous injection (0.011 mg/kg), sublingual suspension (1 mg/kg, prepared from either commercial tablets or peptide powder), and oral tablets (1 mg/kg and 20 mg/kg). Semaglutide was detectable in plasma within 2 minutes post-dosing in all groups except the oral 1 mg/kg group. Sublingual administration demonstrated lower variability in plasma concentrations compared to oral dosing. At 1 mg/kg, the sublingual route achieved a significantly higher area under the curve (AUC) than oral (82.53 vs.15.08 ng*h/ml, p=0.004), indicating improved bioavailability. The maximum plasma concentration (Cmax) was reached within 30 minutes for oral and sublingual routes, and at 8 hours for subcutaneous injection. The relative bioavailability was 0.06% for oral 1 mg/kg, 0.16% for oral 20 mg/kg, and 0.34% and 0.29% for sublingual 1 mg/kg using tablets or powder, respectively. No significant difference in AUC was observed between sublingual semaglutide prepared from oral tablets versus powder. These results highlight the potential of sublingual delivery of semaglutide and suggest this route may improve absorption while reducing variability. This proof-of-concept study supports further development of sublingual semaglutide formulations and pharmacokinetics research in humans.

No abstract available

The aim of this study was to design a poorly water-soluble electrostatic nanocomplex of semaglutide (SMG) with protamine sulfate (PS) and zinc ions (Zn) for prolonged subcutaneous delivery. Complexation of SMG with the cationic peptide PS increased the lipophilicity (logP) proportionally from −4.7 to 0.3, particularly in the presence of Zn. The optimized nanocomplex exhibited spherical morphology, an amorphous state, a particle size of 196.0 nm, and a zeta potential of −45.7 mV. In an in vitro dissolution test under sink conditions, native SMG showed rapid drug release with 98% dissolution within 24 h. In contrast, the nanocomplexes showed markedly delayed release, with a concentration-dependent relationship between PS/Zn contents and SMG release rate, exhibiting 19% drug release over 7 days in the optimized formula. These findings suggest that the proposed nanocomplex is a promising system for long-acting injectable delivery of SMG, potentially enhancing patient compliance in patients with obesity or type 2 diabetes.

Type 2 diabetes mellitus is a major global metabolic disorder requiring long-term and effective therapeutic management. Conventional antidiabetic drugs are often associated with adverse effects and limited patient compliance. Peptide-based therapies, particularly glucagon-like peptide-1 (GLP-1) receptor agonists, have emerged as promising alternatives. Semaglutide, a lipidated GLP-1 analog with prolonged half-life, offers effective glycemic control along with additional benefits in weight reduction and cardiovascular risk improvement. This review highlights the development of various drug delivery systems for semaglutide, focusing on its pharmacodynamics, pharmacokinetics, and formulation strategies. Currently available formulations include once-weekly injectable forms and the first oral GLP-1 receptor agonist enabled through absorption enhancers. However, challenges such as low oral bioavailability and enzymatic degradation persist. Recent advances in controlled-release and nano- based delivery systems, including nanoparticles, liposomes, microspheres, and self-emulsifying formulations, have shown potential in enhancing stability, permeability, and sustained drug release. Continued innovation in delivery technologies may further improve therapeutic efficacy and patient adherence in diabetes and obesity management.”

Desmopressin acetate (DDAVP), a nonapeptide drug, is easily destroyed by heat in the manufacturing process of orodispersible film (ODF). A new challenging study was conducted to improve thermal stability through glycosylation and hydrogen bonding using carbohydrate gums (agar, arabic gum, carrageenan, xanthan gum) using the solvent casting method. Among gum types, xanthan gum strongly showed dual stabilizing effects of DDAVP via covalent glycosylation and hydrogen bonding, minimizing total impurities and optimizing physicochemical properties of ODF under accelerated conditions for six months. The optimized ODF formulation (O-DDAVP ODF) at a DDAVP and xanthan gum ratio of 1:1.5 had a pharmaceutically equivalent dissolution profile as compared with a commercial 0.2 mg commercial Minirin® tablet in four different media: pH 1.2, pH 4.0, and pH 6.8 buffers and deionized water. Furthermore, O-DDAVP ODF showed in vivo bioequivalence to Minirin® tablets in healthy human volunteers. Glycosylation-oriented stabilization of peptide drug using pharmaceutically active excipients against thermal denaturation could be challenged to design patient-friendly ODF.

Among natural sources, guava leaf oil (GLO) has emerged as a potential anticancer agent. However, its limited water solubility poses a significant challenge for its use. Oil-in-water nanoemulsions are used to address the limitation of water solubility of GLO prior to its incorporation into orodipersible films. Nanoemulsions containing GLO:virgin coconut oil (VCO) at a ratio of 50:50 to 70:30 presented a small droplet size of approximately 50 nm and a relatively low zeta potential. GLO:VCO at a ratio of 70:30 was selected for incorporation into sodium alginate film at various concentrations ranging from 1% to 30% w/w. Tensile strength and elongation at break relied on the concentration of nanoemulsions as well as the internal structure of films. Fourier transform infrared spectroscopy revealed that GLO was compatible with sodium alginate. Film containing 2% w/w of nanoemulsions (2G_ODF) exhibited effective in vitro antioral cancer activity, with an IC50 of 62.49 ± 6.22 mg/mL; furthermore, its anticancer activity showed no significant difference after storage at 25 °C for 1 year. Moreover, 2G_ODF at IC60 arrested colony formation and cell invasion. There is also evidence that cell death occurred via apoptosis, as indicated by nuclear fragmentation and positive Annexin-V staining. These findings highlight the potential of orodispersible films containing GLO nanoemulsions as a prospective oral anticancer agent.

No abstract available

Background Oral strip is very similar to thin strip of postage stamp in shape, size and thickness. The strip is designed to be placed on the tongue or any oral mucosal tissue which immediately gets wet and hydrated after being in contact with the saliva. Desloratadine is one of the better-known second-generation antihistamines that has been studied for being effective in relieving the allergic nasal and skin symptoms. Objective The aim of this study is to develop desloratadine orodispersible film (ODF) with fast disintegration time and suitable mechanical strength to treat allergic symptoms in geriatric patients in order to increase compliance and convenience. Methods Solvent casting method using hydroxypropyl methylcellulose (HPMC) as the film forming polymer was applied. Polyethylene glycol 400 (PEG 400) and glycerol (Gly) were used as the plasticizers and citric acid (CA) was used as saliva stimulating agent. The resultant films were evaluated for disintegration time, folding endurance, surface pH, weight variation, thickness, surface morphology using scanning electron microscopy, drug content, content uniformity, moisture loss, moisture uptake, and drug-excipient compatibility using DSC and FT-IR. Results All the selected films started to disintegrate in less than 14 seconds. Selected optimum films exhibited good mechanical properties with a folding endurance value greater than 100. The uniformity in weight, thickness, and drug content in the selected films was obtained. Surface pH was within the normal range (6.4 - 6.8). A smooth surface of the films was obtained and drug-excipient compatibility was proved using DSC and FT-IR. The dissolution test was done for optimum film formulations by simulating the oral cavity physiological conditions using the conventional dissolution test apparatus. More than 87% of the drug was released by the 4th minute. Conclusion Orodispersible film of desloratadine was successfully prepared by solvent casting method in order to improve the disintegration/dissolution of the drug in oral cavity and hence better patient compliance and effective therapy.

This study evaluated a new orodispersible film (ODF) containing a homogeneous donepezil-free base (DPF), which is used as a treatment for Alzheimer's disease. DPF causes problems, such as layer separation and non-homogenization in ODF solutions, because of its insolubility. This study attempted to improve the dispersion stability of DPF using thickeners, nonionic surfactants, and vinyl polymer to solve this problem. DPF was homogenized within ODF when 0.24% of polyvinyl alcohol was added. The comparative dissolution of the test drug and reference drug in water, pH 1.2, 4.0, and 6.8 revealed similarity factors of 65.2, 59.4, 52.4, and 61.8, respectively, showing that they were equivalent. The test drug was stable under Zone II for 12 months, maintaining a content of more than 99%. In addition, there was no change in the appearance and dissolution rate. Furthermore, a bioequivalence study between the test drug and reference drug confirmed that they were equivalent in standards for confirming bioequivalence (AUCt and Cmax). The homogenized ODF can be produced by adding vinyl polymer to the insolubility drugs, and it is expected to be useful in research on insoluble drug formulations.

Pediatric emesis is a common and clinically significant problem associated with acute gastroenteritis, postoperative nausea, motion sickness, systemic infections, and drug-induced adverse effects. In children, recurrent vomiting may rapidly lead to dehydration, electrolyte imbalance, poor oral intake, reduced therapeutic compliance, and increased risk of hospitalization. These challenges highlight the need for age-appropriate, patient-centric antiemetic delivery systems that are effective, acceptable, and easy to administer. Conventional dosage forms, including syrups, tablets, and capsules, often fail to meet these requirements because of poor palatability, swallowing difficulties, dose inaccuracy, and administration challenges during active vomiting. Orodispersible films (ODFs) have emerged as a promising alternative owing to their rapid disintegration in the oral cavity, water-independent administration, ease of handling, portability, and potential for improved pediatric acceptability. Their formulation can be tailored through selection of suitable polymers, plasticizers, sweeteners, saliva stimulants, and taste-masking approaches to optimize drug release and patient compliance. This review highlights the clinical burden of pediatric emesis, examines the limitations of conventional antiemetic therapy, and discusses the growing rationale for ODF-based pediatric delivery systems. Particular attention is given to the need for age-appropriate formulations in children and the therapeutic advantages of film-based systems in improving medication adherence and ease of administration. Overall, ODFs represent a promising platform at the interface of pediatric clinical need and modern formulation science, with substantial potential to improve antiemetic therapy in children. Keywords: Pediatric emesis; orodispersible films; pediatric drug delivery; antiemetic therapy; age-appropriate formulations; oral thin films

The current work focused on the formulation and in vitro evaluation of Lemborexant oral dispersible films (ODFs) loaded with nanoparticles to improve solubility, dissolution, and patient compliance in the treatment of insomnia. Lemborexant, a dual orexin receptor antagonist, has low water solubility, reducing its oral bioavailability. To overcome this limitation, nanoparticles were prepared using the solvent displacement method and incorporated into fast-dissolving polymeric films that contained hydroxypropyl methylcellulose (HPMC) and carboxymethyl cellulose (CMC) as film-forming agents, PEG as a plasticizer, and superdisintegrants for rapid disintegration. The produced films were tested for physicochemical and mechanical properties such as thickness, weight fluctuation, folding endurance, tensile strength, surface pH, drug content homogeneity, disintegration time, and in vitro drug release.The optimized formulation demonstrated uniform thickness and weight, as well as appropriate tensile strength. The films disintegrated quickly (15-30 seconds) and had considerably higher in vitro drug release than pure Lemborexant. FTIR tests verified the absence of drug-excipient interactions, while SEM revealed homogeneous nanoparticle dispersion. The findings suggested that Lemborexant-loaded nanoparticle oral dispersible films are a viable delivery platform for quick onset of action, increased bioavailability, and enhanced patient compliance, particularly in geriatric patients with swallowing issues. Additional in vivo investigations are needed to confirm the therapeutic efficacy and pharmacokinetic advantages of the proposed formulation. Keywords: Lemborexant, Oral Dispersible Film, Nanoparticles, Solvent Casting, In vitro drug release studies.

No abstract available

Objective: The present study was done to understand the effect of formulation variables on the quality of orodispersible films using quality by design (QbD) approach as mentioned in ICH Q8 (R2) guideline.Methods: A definitive screening design of experiments (DoE) was used to identify and classify the critical formulation variables affecting critical quality attributes (CQA) using 2×2 factorial design. Based on prescreening study, the critical formulation variables, i.e. concentration of film-forming polymer and plasticizers (propylene glycol and polyethylene glycol 400 [PEG 400]) were kept in the range of 1.5–2.5% w/w and 0.5–1% v/v, respectively. A total of eight laboratory-scale formulations were prepared which were provided by DoE using solvent casting method. These batches were evaluated for CQA’s, i.e. mechanical properties such as folding endurance (FD) and disintegration time (DT). Data were analyzed for elucidating interactions between two variables and for providing a predictive model for the process. Finally, the drug was incorporated into optimized batches, and these were evaluated for in vitro dissolution study in simulated saliva (pH 6.8) as well as their mechanical properties.Results: The results suggested that the concentration of film-forming polymer and plasticizer was critical to manufacture orodispersible film with desired CQA, i.e. mechanical property (FD [>150 folds]) and DT (<60 s). The percent drug release, FD, and DT of optimized Formulation I (hydroxypropyl methylcellulose [HPMC] E5 (2%) and propylene glycol [0.15 mL]) were found to be 82.13%±0.260 (in 15 min), 164±2, and 49±1.5 s, respectively, and for optimized Formulation II (HPMC E5 [2%] and PEG 400 [0.15 mL]) was found to be 64.26%±2.026 (in 15 min) and 218±6 and 55±4 s, respectively.Conclusion: From the results, it has been found that the percentage drug release of naratriptan hydrochloride containing propylene glycol as a plasticizer was greater than the formulation containing PEG 400 as plasticizer. From this, we concluded that QbD is very much useful approach to get an optimized formulation in an economic and faster way in comparison to traditional method (hit and trail methods). The futuristic application of the film will involve the management of an acute migraine.

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Objective: The aim of this investigation is to formulate, design, optimize and to an evaluation of the rapid soluble orodispersible film (OTF) of dipyridamole (DPI) using the solvent casting method by 32 central composite designs. Methods: Statistical design was used to optimize the preliminary formulations by selecting independent variables such as a polymer (HPMC-E52V, X1) and plasticizer (PEG400, X2) concentration as film-forming polymer and as a plasticizer and the dependent variables such as the release of drug in percentage (Y1), time of disintegration (sec, Y2) and tensile strength (N/m2 Y3). Results: The content of the drug was resulted in the range of 95.05–101 %. The physical properties were found to be colorless and homogenously clear and smooth surface. The folding endurance shown as without any scratches with the pH ranges from 6.35 to 6.75 and the prepared film was not irritated to the oral mucosa. Conclusion: The prepared films showed an optimum time of disintegration that is 25 sec, 96.74% drug release in phosphate buffer of pH 6.8 at initial 5 min and 85.98 % ex-vivo permeation studies after 30 min.

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The aim of this study was to prepare sodium glycocholate liposomes (SGC-Lip) encapsulating semaglutide (Sml) to improve oral bioavailability and better exert hypoglycemic effect. In this paper, SGC-Lip was prepared by reverse-phase evaporation method with particle size around 140 nm, potential around -27 mV, rounded morphology and better stability. The hypoglycemic and intestinal uptake effects of SGC-Lip and cholesterol-containing liposomes (CH-Lip) were comparatively investigated in rats, and the oral safety of SGC-Lip was examined by cytotoxicity assay. The results indicate that SGC-Lip can achieve a hypoglycemic effect of 40% of the initial value within 12 hours, and the AAC0-12h is approximately six times that of CH-Lip without sodium glycocholate. The results of the cytotoxicity tests indicate that SGC-Lip has good oral safety. SGC-Lip enhances the absorption of semaglutide in the small intestinal villi via an apical sodium-dependent bile acid transporter (ASBT)-mediated pathway with the highest penetration at the ileal site. In summary, the oral bioavailability of semaglutide can be improved by encapsulating semaglutide in SGC-Lip and utilizing the stabilizing and permeation-promoting effects of SGC on liposomes.

Purpose: Sodium N-[8-(2-hydroxybenzoyl)amino]caprylate (SNAC) is a well-known penetration enhancer widely used in commercial applications. This study aims to broaden its properties through a novel strategy of converting it into its phenolate salts. The objective is to investigate the synthesis of SNAC phenolate salts, specifically SNAC–choline (SNAC-CH), SNAC–sodium (SNAC-Na), and SNAC–phosphatidylcholine (SNAC-PC), and to explore their potential application in improving the oral absorption of semaglutide. Methods: The synthesis of SNAC phenolate salts was confirmed through 1H-NMR, FTIR, and an elemental analysis of C, H, N, and O. In vivo testing was conducted to assess the oral delivery of semaglutide using these synthesized SNAC phenolate salts. Pharmacokinetic (PK) values were measured to evaluate the impact on drug absorption. Results: The synthesis of SNAC phenolate salts (SNAC-CH, SNAC-Na, and SNAC-PC) was successfully achieved under appropriate conditions, and their structures were confirmed using analytical techniques such as IR, NMR, and CHN elemental analysis. The paradigm of their use was evaluated through an oral pharmacokinetic (PK) in vivo study using SNAC phenolate salts, which did not impair the original SNAC PK values. This suggests that this strategy holds promise as a potential new effective enhancer for oral absorption. Conclusions: The utilization of SNAC phenolate salts presents a novel and promising strategy for extending the verity of penetration enhancers’ molecules and properties. Synthesizing phenolate salts represents a new chemical strategy that may open new avenues in molecular development. This approach holds future potential to enhance the oral delivery of peptide drugs like semaglutide without compromising therapeutic efficacy. Overall, it offers significant advancements in the field by providing a potential alternative to injectable peptides through oral delivery systems.

Abstract Objectives In this study, the comparative bioavailability of semaglutide following the administration of oral (PO) and subcutaneous (SC) doses in healthy subjects was evaluated. The pharmacokinetics of semaglutide of these formulations at lower doses (SC dose of 0.25 mg; PO dose of 3 mg) was examined by utilizing a sensitive bioanalytical method. Methods Twenty-two subjects were administered either 0.25 mg SC or 3 mg PO and blood samples were taken up to 504 h. The samples were assayed for semaglutide with an analytical range of 0.05–50 ng/mL. The pharmacokinetic parameters were estimated using a non-compartmental approach and were used to evaluate the comparative bioavailability of semaglutide. Results The pharmacokinetics of semaglutide was characterized following the administration of low subcutaneous and oral doses. The comparative bioavailability (PO relative to SC) was 0.66 % at the doses administered. Overall, the study drug was well tolerated, and no serious adverse events were reported. Conclusions The bioavailability of semaglutide following oral and subcutaneous administrations has been determined using a validated bioanalytical method. This method will enable more investigations into the pharmacokinetics of all formulations of semaglutide at lower doses, which will enable a better understanding of its’ disposition in healthy subjects and in patients.

Nanoparticles (NPs) modified with glycocholic acid (GCA) at surfaces are considered promising tools to overcome oral drug delivery barriers. However, question on the influence of surface GCA density over delivery efficiency arises due to ligand-induced changes in surface properties of NPs. To answer this question, we engineered GCA-modified nanoparticles (GCA NPs) with different surface densities, and their surface hydrophobicity, mucus penetration, cellular uptake, apparent permeability coefficient (Papp), intracellular trafficking behavior and oral bioavailability were compared. The results turned out that GCA NPs were found with increased surface hydrophobicity, which limited their transport across mucus layer. Nanoparticles with 50 % surface GCA density (50 % GCA NPs) demonstrated optimal performance. Compared to 100 %GCA NPs, 50 %GCA NPs exhibited an 83.28 % improvement in mucosal penetration capability, while a 250.67 % increase in cellular uptake was noticed when comparing with PEG NPs. Overall, the 50 % GCA NPs significantly enhanced trans-epithelial transport across Caco-2/E-12 co-cultured monolayers, achieving a Papp value of 3.30 × 10-6 cm/s, while the Papp values of 100 %GCA NPs and PEG NPs were 2.23 × 10-6 cm/s and 1.73 × 10-6 cm/s. In vivo studies confirmed their therapeutic potential: oral administration of semaglutide (SMG)-loaded 50 % GCA NPs increased systemic SMG bioavailability to 12.12 %, achieving sustained glycemic control in type 2 diabetic rats. The optimized formulation exhibited favorable safety profiles and prolonged pharmacological effects. This study establishes a critical equilibrium between enhanced mucosal penetration and ligand-receptor interaction, while mitigating intracellular retention issues associated with high-density GCA-functionalized nanoparticles. These findings indicate that attentions should be paid in ligand-associated surface property alterations, which could exert unexpected influence on the performance of NPs constructed for oral peptide drug delivery.

The change of injectable semaglutide into verbally administered portion of drug or other consumable forms shows a significant progress in peptide-located diabetes medicines. This study evaluates the feasibility, pharmacokinetics, and temporary balance of oral semaglutide brought through capsule and liquid formulations in Sprague–Dawley rats. Injectable semaglutide (1 mg/mL) was reformulated using SNAC-located next-release sciences. Both oral formulations illustrated agreeable bioavailability (0.8–0.9%) relative to the injectable form. Pharmacokinetic reasoning told deferred Tmax for the tablet distinguished to the liquid, unpaid to formulation excipients. Stability experiment over 30 days designated maintained potency (95–97%) accompanying gentle opalescence in the liquid expression, inciting plans for enhanced expression plannings. These judgments provide basic evidence advocating future long-term ICH-obedient support studies and expression refinement for numbering spoken GLP-1 agonist development.

The present review will provide an overview of orally fast dissolving films. The most popular oral dosage forms are oral fast-dissolving films, which dissolve in the mouth in a matter of seconds without the need for water consumption and provide a quick onset of action. Because of their flexibility and ability to comply with patients, these drug delivery systems are primarily used for pediatric and geriatric patients. They release the active pharmaceutical ingredient within the mouth as soon as they come into contact with saliva. A rapidly dissolving oral dosage form that can be used for drugs with low bioavailability and high first pass metabolism. Oral films are formulated using polymers, plasticizers, colors, flavors and sweeteners etc. Solvent casting, hot melt extrusion, rolling, and solid dispersion techniques are used in the production of the oral film. This review compiles the most recent developments in the formulation of fast-dissolving films and their evaluation metrics, such as thickness, disintegration time, folding endurance, and in-vitro dissolution. It also highlights some of the marketed products to demonstrate the market's demand for oral fast-dissolving films. Also, go over a few of the difficulties encountered during the creation of fast-dissolving films. Keywords: Fast dissolving film, Solvent casting method, film forming polymer, Evaluation

Background: This review examines the technology and therapeutic potential of oral dissolvable strips (ODS) loaded with micellized active pharmaceutical ingredients (APIs) for improved systemic drug delivery. Oral dissolvable strips (ODS) have emerged as a convenient and patient friendly route for drug delivery; however, many APIs exhibit poor aqueous solubility and stability, limiting their therapeutic efficiency. Micellar nanocarriers embedded in ODS can overcome these limitations by improving the solubility, stability, pharmacokinetics, and bioavailability. Objective: This review evaluates the integration of micelle technology with ODS platforms to improve systemic absorption and therapeutic performance of APIs, focusing on formulation advances, pharmacokinetic improvements, and translational challenges. Methods: Peer-reviewed research articles, patents, and reviews related to micellized APIs and oral film drug delivery systems were analyzed to identify formulation strategies, physicochemical optimization approaches, and clinical implications for diverse APIs. Results: Micelle-embedded oral films enable efficient delivery of hydrophobic drugs, produce faster absorption and achieve higher plasma concentrations than conventional oral routes. By improving patient compliance, minimizing toxicity, and protecting APIs from hepatic and gastrointestinal degradation, micelle/ODS systems significantly enhance bioavailability. Challenges exist with formulation variables such as micelle composition and film thickness which affect release kinetics, and optimization and stabilization of micellized APIs. Conclusion: Integrating micellar nanotechnology with oral dissolvable strips represents a promising next-generation platform for effective, non-invasive, and patient-compliant oral drug delivery. This technology holds great potential for delivering prescription drugs, supplements, chemotherapeutics, and biologics. Future investigations should prioritize optimizing formulation strategies and scalable manufacturing processes, clarifying regulatory pathways, and designing clinical trials. Keywords: micelle, oral dissolvable strip, bioavailability, pharmacokinetics, drug delivery

The FDOFs have become one of the potential alternative drug delivery systems as it has been shown to increase the rate of dissolution, productivity of bioavailability and has also provided better convenience to patients particularly those with swallowing challenges. This paper set out to design, optimize and characterize the rapid-dissolving oral films with a model drug using the solvent-casting method. The different formulations were made through varying the polymer concentration, plasticizer content and superdisintegrant ratio to identify their effect on physicochemical and mechanical characteristics. It was tested on the basis of thickness, surface pH, endurance of folding, weight change, drug contents, disintegration time, tensile strength, and in-vitro drug release. Findings established that all formulations possessed acceptable physical and mechanical properties and the optimized film had uniform thickness (0.095 mm), acceptable tensile strength (16.2 N/mm2), excellent elongation (29%) and perfect surface pH (6.6). Optimized formulation had a rapid disintegration period of 15 seconds which guaranteed rapid dispersion in the oral cavity. In-vitro dissolution tests showed that there was greatly improved drug release by the optimized film with 94 and 99 percent release after 5 and 10 minutes respectively with the pure drug releasing very slowly. The results are a good foundation to prove that FDOFs can significantly enhance drug dissolution and potentially bioavailability. All in all, the research proves that fast-dissolving oral movies are an effective, patient-friendly, and efficient dosage to help the drug achieve a rapid onset of action. It is also suggested that the performance of the newly developed device should be assessed under in-vivo conditions and that stability issues should be tested in the long run.