阿奇霉素 掩味 干混悬剂

Azithromycin (AZI) is one of the most commonly used macrolide antibiotics in children, but has the disadvantages of a heavy bitter taste and poor solubility. In order to solve these problems, hot-melt extrusion (HME) was used to prepare azithromycin amorphous solid dispersion. Preliminary selection of a polymer for HME was conducted by calculating Hansen solubility parameter to predict the miscibility of the drug and polymer. Eudragit® RL PO was chosen as the polymer due to its combination of taste-masking effect and dissolution. Moreover, the solubility was improved with this polymer. Design of experiments (DoE) was used to optimize the formulation and process, with screw speed, extrusion temperature, and drug percentage as independent variables, and content, dissolution, and extrudates diameter as dependent variables. The optimal extrusion parameters were obtained as follows: temperature—150 °C; screw speed—75 rpm; and drug percentage—25%. Differential scanning calorimetry (DSC) and Powder X-ray Diffraction (PXRD) studies of the powdered solid dispersions showed that the crystalline AZI transformed into the amorphous form. Fourier transform infrared spectroscopy (FTIR) results indicated that the formation of a hydrogen bond between AZI and the polymer led to the stabilization of AZI in its amorphous form. In conclusion, this work illustrated the importance of HME for the preparation of amorphous solid dispersion of AZI, which can solve the problems of bitterness and low solubility. It is also of great significance for the development of compliant pediatric AZI preparation.

Abstract This research aims to develop bitter taste-masking microcapsules containing azithromycin (AZI) by a simpler and familiar method, fluid-bed coating technology, in comparison with Zithromax®. Cores of microcapsules, AZI microparticles, were prepared by fluid-bed granulation, then taste-masking polymer was covered on by fluid-bed coating technique. Eudragit L100, Eudragit RL100, and ethyl cellulose in single and combined with Eudragit L100 and Eudragit E100 were used as taste-masking polymers. The obtained microcapsules were characterised by taste-masking ability, in vitro release, SEM, coating thickness, and coating efficiency. Combination of ethyl cellulose and Eudragit E100 (3:1) in coating thickness of 45.13 ± 2.12% w/w prevents AZI release from microcapsules below bitter taste threshold (1.78 ± 1.17 µg/ml). Bioavailability of powders containing AZI microcapsules and pH modulators (50 mg Na3PO4 and 35 mg Mg(OH)2) was not significantly different from the reference product (Zithromax®, Pfizer, New York, NY) in the rabbit model (p > 0.05). These results support the possibility of developing a generic product containing AZI.

… In this study, azithromycin (AZI) a broad spectrum antibacterial drug and highly active against gram-negative organisms26-29 was used as a model drug. Methacrylic acid (MAA)-based …

Background The obnoxious bitter taste of orally taken antibiotics is one of the biggest problems in the treatment of children. The pediatric population cannot tolerate the bitter taste of drugs and vomit out which ultimately leads to suboptimal therapeutic value, grimace and mental stress so it is the challenging task for the formulation scientists to formulate a palatable formulation particularly to overcome address the issue. Purpose of study The study aimed to mask and evaluate the unpleasant bitter taste of azithro-mycin (AZ) in the dry suspension dosage form by physisorption technique. Materials and methods AZ was selected as an adsorbent and titanium dioxide nanoparticles as adsorbate. The AZ nanohybrids (AZN) were prepared by treating fixed amount of adsorbent with a varied amount of adsorbate, prepared separately by dispersing it in an aqueous medium. The mixture was sonicated, stirred followed by filtration and drying. The AZN produced were characterized by various techniques including scanning electron microscopy (SEM), energy dispersive X-rays (EDX), powder X-ray diffraction (PXRD), HPLC and Fourier-transformed infrared (FTIR). The optimized nanohybrid was blended with other excipients to get stable and taste masked dry suspension dosage form. Results The results confirmed the adsorption of titanium dioxide nanoparticles on the surface of AZ. The fabricated optimized formulation was subjected for taste masking by panel testing and accelerated stability studies. The results showed a remarkable improvement in bitter taste masking, inhibiting throat bite without affecting the dissolution rate. The product showed an excellent stability both in dry and reconstituted suspension. The optimized formulation of AZN and was found stable when subjected to physical and chemical stability studies, this is because of short and single step process which interns limits the exposure of the product to various environmental factors that could potentially affect the stability of the product. The dissolution rate of the optimized formulation of AZN was compared with its marketed counterpart, showing the same dissolution rate compared to its marketed formulation. Conclusion The current study concludes that, by fabricating AZ-titanium nanohybrids using physisorption can effectively mask the bitter taste of the drug. The palatability and stability of azithromycin formulation was potentially enhanced without affecting its dissolution rate.

… The aim of this study was to formulate bitter taste masking microparticles containing azithromycin and incorporate these microparticles into dispersible tablets. The obtained DTs-MP …

Abstract Introduction and purpose The unpleasant extremely bitter taste of the orally administered broad-spectrum antibiotic azithromycin decreases patient compliance, especially in pediatrics. This issue can be overcome by decreasing drug interaction with the tasting buds using insoluble polymers at salivary pH (6.8 − 7.4), like the cationic polymer Eudragit EPO. Supercritical fluid technology is a green synthesis method for preparing pharmaceutical preparations that replace organic solvents with safe supercritical CO2. This study aimed to mask the bitter taste of azithromycin using the supercritical fluid method and a pH-sensitive Eudragit EPO polymer. Methods A foaming process was investigated for preparing a formulation (TEST), which comprises treating the polymer with supercritical carbon dioxide (CO2) fluid to prepare a taste-masked dosage form without employing organic solvents or flavors. Results The use of the supercritical technique at 40 °C and 10 MPa for 2 h allowed the manufacturing of solvent-free polymeric foam with azithromycin dispersions; the average calculated percentage of apparent volume change was 62.5 ± 5.9% with an average pore diameter of 34.879 Å. The formulated sample showed low drug release in simulated salivary fluid while keeping its crystalline nature. Moreover, clinical studies on healthy subjects showed that the formula successfully masked azithromycin’s bitter taste. Conclusions Overall, it has been shown herein that the supercritical fluid technology foaming method is promising in masking the bitter taste of bitter ingredients. Graphical Abstract

We aimed to develop a novel method for assessing the bitterness of azithromycin-containing reverse micelles (AM-containing RMs). Azithromycin-containing reverse micelles were prepared by processing Lipoid E80 and medium chain triglycerides via a freeze-drying method. The bitterness threshold of azithromycin was determined by human taste test, and an equation was derived to correlate the azithromycin concentrations and bitterness scores of standard solutions. Simulated salivary fluids and sampling times were fixed based on the drug release profile of AM-containing RMs, with Zithromax® (a commercial formulation of azithromycin) used as the control. The drug release concentrations from stimulated salivary fluids were then used to assess the bitterness of AM-containing RMs and Zithromax®. Afterward, the oral bioavailability of both formulations was evaluated by in vivo experiments in male Wistar rats. The results showed that the bitterness threshold of azithromycin standard solutions was between 25.3 µg/ml and 30.4 µg/ml. Thereafter, we calculated that the bitterness scores and the drug release concentrations of the azithromycin-containing reverse micelle formulation were similar to those of Zithromax® at each time point after 10 min of dispersal in simulated salivary fluid. In addition, the AUC0−t after oral administration of AM-containing RMs was 1.75-fold (P < 0.05) higher than that of Zithromax®. In conclusions, a system for assessing bitterness was developed using an in vitro drug release evaluation method and a human taste test panel. We found that the bitterness of azithromycin was successfully masked by reverse micelles, which also improved the oral bioavailability of azithromycin compared to that of Zithromax®.

The aim of this study was to prepare a microsphere formulation in order to mask the bitter taste of azithromycin. Microspheres of azithromycin with ethyl cellulose were prepared by the modified solvent diffusion method. The microspheres were mixed with other excipients to form orally dry suspensions and the sensory test for taste masking was evaluated. Results demonstrated that the suspension could significantly mask the bitter taste of azithromycin and the relative bioavailability of suspensions to reference preparations was 102.7%. The results indicate that the microsphere formulation can be a promising drug carrier for masking the bitter taste of azithromycin.

Despite the broad spectrum of the antibiotic Azithromycin, its extremely bitter taste after oral dosing decreases patient compliance. This bitter taste can be masked by minimizing Azithromycin interaction with the tasting buds using polymers that are insoluble at salivary pH (6.8–7.4), like the cationic polymers Eudragit EPO and Eudragit S100. The purpose of this study was to employ two different techniques (solvent evaporation (SE) and supercritical fluid technology (SFT)) for encapsulating Azithromycin into Eudragit microparticles to mask its bitter taste. The formulations were characterized using Fourier-transform infrared spectroscopy (FTIR(, powder X-ray diffraction (PXRD), Differential scanning calorimetry (DSC), and scanning electron microscope (SEM). Also, the Azithromycin in vitro release and in vivo assessment of bitter taste masking were conducted. The present work showed promising results in veiling the bitter taste of Azithromycin. Taste panel scores for the in vivo clinical taste study of the formulation prepared using SE was 0.3 after 30 seconds compared to Azithromycin, resulting in a score of 3 owing to its palpable bitter taste. Whereas drug-Eudragit EPO showed no interaction, FTIR results indicated azithromycin interaction with Eudragit S100. The formulation prepared by the SE method and Eudragit EPO showed efficient taste masking, within-matrix encapsulation, lower drug release in simulated salivary fluid (SSF, <2% released over 60 seconds), and loss of Azithromycin’s crystallinity. On the contrary, SFT had higher encapsulation efficiency (91%) but faster in vitro release (6% released over 60 seconds). Thus, SE was better than SFT in Azithromycin taste masking using Eudragit EPO.

Azithromycin (AZI) is a commonly used antibiotic with extremely bitter taste that severely decreases the compliance of patients. Besides, the poor solubility of AZI in alkaline pH makes it difficult to be absorbed in the small intestine. To achieve the dual effects of taste masking and enhanced absorption, AZI-loaded pellets were coated by polymer blend of Eudragit®RL30D and Eudragit®L30D-55. The coated pellets could avoid drug release in the oral environment (pH 5–7) but release rapidly in the gastric environment (pH 1–3). Then, the coated pellets were further formulated into dry suspension to address the problem of dysphagia. The taste-masking effect tests by electronic tongue and human volunteers revealed that the dry suspension was more effective to improve the bitter taste of AZI than the commercial product. Therefore, this study provided an economical and feasible approach for taste masking with good practical application prospect.

Azithromycin, a macrolide antibiotics, is one of the frequently used drugs in the children and elder. However, due to these population difficulty in swallowing and inefficient absorption, and azithromycin inherent poor solubility, bitter taste, and instability in the stomach acidic condition, it is a challenge to reach high oral bioavailability of this drug. To overcome these issues, we developed and characterized the effervescent granules containing azithromycin solid dispersion. Firstly, the solid dispersion was prepared, employing both wet grinding and solvent evaporation methods, with different types/amounts of polymers. The optimal solid dispersion with β-cyclodextrin at a drug:polymer ratio of 1:2 (w/w), prepared by the solvent evaporation method, significantly enhanced the azithromycin solubility 4-fold compared to the free drug, improved its bitterness from “bitter” to “normal”, possessed intermolecular bonding between the drug and polymer, and transformed the azithromycin molecules from crystalline to amorphous state. Secondly, the effervescent granules incorporating the solid dispersion were formulated with varied excipients of sweeteners, gas-generators, pH modulators, and glidants/lubricants. The optimal formula satisfied all the properties stated in the Vietnamese Pharmacopoeia. In summary, the final effervescent granules product could be further investigated in in-vivo and in clinical settings to become a potential azithromycin delivery system with high bioavailability for the children and elder.

… azithromycin suspension, enhancing their acceptability in pediatric applications. Although the alkaline nature of the vehicle reduced acid-induced degradation of azithromycin … and taste …

Abstract The present work aimed to formulate azithromycin as amorphous solid dispersion for bitter taste masking, improving stability in an acid medium, and reducing the side effects. Solid dispersion with pH-dependent polymers (Eudragit L100, Eudragit S100) were prepared by the solvent evaporation method. The influence of polymer and drug-polymer ratio on production yields and loading% were evaluated. The F2 (AZI: L100 1:4) that gave the highest yield and loading (96 ± 0.3, 92.3 ± 0.07 respectively) was examined using Scanning electron microscopy (SEM), Fourier transform infrared (FT‑IR), Powder X‑ray diffraction (PXRD) and Differential scanning calorimetry (DSC). Taste masking evaluation was performed in vitro by two methods (in vitro drug release at saliva pH, and comparison of bitter taste threshold with the optimal formulation). (FT‑IR) study displayed that there was no interaction happen between azithromycin and Eudragit L100. DSC and PXRD emphasized the conversion of azithromycin from the crystalline to the amorphous form and entrapped inside the solid dispersion. In vitro, taste assessment detected no azithromycin release in salvia pH (6.8) within 5 min and minimal release in pH 1.2 which indicate this method might be a suitable approach to achieve taste masking of AZI and to improve stability in acid conditions.

Purpose: To prepare azithromycin (AZI) sustained-release suspension containing AZI-coatedmicrocapsules (AZI-CM) impregnated with AZI-drug resin complex (AZI-DRC), in order to mask thebitter taste of AZI and improve the oral compliance of patients.Methods: The AZI-DRC was prepared using the bath method, with cation exchanger resinAmberlite®IRP64 as a drug carrier, and it was characterized using scanning electron microscopy(SEM), x-ray diffraction (XRD) and Fourier transform infrared (FTIR) spectroscopy. Pretreated AZI-DRCwas coated using emulsification-solvent evaporation method to achieve sustained-release effect. Theeffect of coating on in vitro drug release of the microcapsules was investigated to obtain the optimalAZI-CM through single-factor investigation. The optimized AZI-CM formulation was further dispersed inthe optimized suspension matrix to obtain AZI sustained-release suspension. Then, thepharmacokinetics of AZI sustained release from the suspension was studied in rats and compared withcommercially available AZI dry suspension.Results: Taste evaluation by volunteers showed that AZI-DRC had a good taste-masking effect on AZI.Results from SEM, XRD and FTIR demonstrated that AZI was present in AZI-DRC solely in amorphousform. Three batches of AZI-CM prepared after optimization produced a significant sustained releaseeffect (p < 0.05). The AZI sustained-release suspension did not change significantly after 10 days and 3months, indicating good stability (F > 0.9; drug release: f2 > 50; drug leakage < 0.5 %). In vivo resultsshowed that AZI sustained-release suspension had a lower Cmax a higher Tmax and a betterbioequivalence than AZI dry suspension available in the market.Conclusion: These findings depict a newly developed AZI sustained-release suspension with improvedbioavailability, sustained-release effect, masked bitterness, and good therapeutic effect.

… The article describes strategy for masking the intensely bitter taste of Azithromycin Dihydrate… Prepared formulation showed good stability and retention of palatable taste. Thus, the “…

… The importance of taste masking and taste evaluation during the … azithromycin or amoxicillin suspensions 18 2 / Cefdinir vs amoxicillin-clavulanate potassium or cefprozil or azithromycin …

Azithromycin is the drug of choice in the treatment of several bacterial infections, most often those causing middle ear infection, bronchitis, pneumonia, typhoid and sinusitis. It’s also effective against certain urinary tract infections and venereal diseases. This study was carried out to prepare an acceptable suspension either as dry physical mixture powder or granules to be reconstituted, through studying the effect of various type and concentration of suspending agent (xanthan gum, hydroxypropyl methylcellulose (HPMC), either alone or in combination) on the release profile of the drug. The best prepared suspension formulas (H& III) were selected depending on the dissolution profile of each formulas and then compared with the reference suspensions (Zithromax and Azi-once).The viscosity, sedimentation volume, Resuspendability and expiration date were evaluated for the chosen formulas (H&III) and compared with references ZithromaxÃ’ and Azi-onceÃ’.The result indicated that the chosen formula – H had better dissolution rate compared with references suspensions, Also it was less viscous than them.While other chosen formula – III had lower dissolution rate compared with ZithromaxÃ’ and higher dissolution rate than AZi – once, also it was less viscous than both references.It was found that the dry physically mixed powder (formula – H) was more stable than the granular suspension (Formula III) since the expiration date for formula H and formula III were 3.24 and 2.7 years respectively.  Key words: Azithromycin, suspending agent, suspension.

Azithromycin is used for the treatment of bacterial infection, mainly used in middle ear infection, typhoid, sinusitis, bronchitis in urinary tract infection and venereal disease. The present study aimed to develop dry or oral reconstitutable suspension to minimize the solubility problem of the drug. It shows the adequate chemical stability of the drug during the shelf life and it avoids the problem of physical stability and solubility of drug. The study was carried out by preparing the dry powder or granules for oral reconstitutable suspension by using suspending agent sodium CMC and acacia on release profile of the drug. The prepared best formulation (F6) was selected depending on its physiochemical properties. The prepared oral reconstitutable suspension was evaluated for the rheological, viscosity, re-suspendibility and sedimentation volume. The formulation of acacia showed excellent sedimentation volume and good re-dispersibility as compared to other formulation. The study was found that the dry physical mixture method showed good stability of the drug.

Background: Concerns have been raised about home storage conditions and the appropriateness of the temperature of the water used to reconstitute azithromycin oral powders. Objective: To investigate the stability of Azithromycin oral suspension using two types of water, at different storage conditions during the recommended in use shelf life. Methods: The analysis was performed using (HPLC). This study was carried out by selection of two brands of Azithromycin dry suspension, exposed to different conditions (refrigerator conditions (2-8°C) and ambient temperature, then the assay test was performed for fourteen days. In addition, physical tests were performed for the samples. Results: HPLC results indicated that the content of Azithromycin decreased in the samples that were exposed to heated water in comparison to the samples exposed to cooled water at ambient temperature. The statistical analysis results of the one way ANOVA indicated that there was no significant difference in the content of the drug in the azithromycin brands. In addition, one way ANOVA results indicated that there was a significant difference (P < 0.05) in the content of the drug in the Azithromycin that was exposed to the various in home storage conditions, namely, refrigerator 2 – 8°c and room temperature 25 – 29°c that were evaluated in the study. Conclusion: The local azithromycin suspension brands demonstrated acceptable stability after reconstitution with cooled distilled water. In addition, storage temperature significantly influences the degradation of the active compound after reconstitution; however, refrigeration is recommended to minimize drug degradation during the recommended use period.

Purpose: The aim of this work was to prepare azithromycin (AZI) nanosuspensions to increase the solubility and dissolution rate. Method: AZI nanosuspensions were prepared by the …

… an azithromycin nanosuspensions by high pressure homogenization and hope to solve the puzzles about the application of azithromycin … suspensions was transferred into freeze-dried …

… The combined suspension formulation for a 2-g dose of azithromycin provided taste-… a suspension. In this process, microspheres were formed by suspending azithromycin dihydrate in a …

… Therefore, the objective of the present study is to determine the stability of the active compound in a reconstituted oral suspension of azithromycin under various in-home storage …

… spray-freeze-drying. Finally, the SFD-SD preparations for this investigation can be used for the formulated drug nano-suspension, needle-free powder or dry powder inhalation (inhaled …

… The filtrate so isolated was treated with suspensions equal volume of acetone which … was dried at 40 Ampicillin trihydrate suspensions were prepared with C for 2 hours. The dried mass …

Dry suspension is commercial dry mixtures that require addition of water at the time of dispensing. The major consequence of the bitter taste is to restrict greatly the further development of oral preparations and clinical applications of these drugs. People wish to take effective drugs that have a nice taste can be administered easily. Accordingly, it is important to mask the unpalatable taste of a drug in order to improve the product quality. The solvent evaporation process is used for microencapsulation which is carried out in a liquid manufacturing vehicle. Eudragit L100 is used as taste masking agent . FT-IR study shows that there is no significant interactions occurring between drug and excipients. The suspension prepared was evaluated for various parameters like sedimentation volume, degree of flocculation, drug content and In-vitro dissolution time. All the parameters were found to be within limits. When the results were compared with marketed preparation suspension was found to be better with respect to marketed preparation.

Given that it influences the therapeutic product's dissolving profile and bioavailability, particle size is a crucial component of contemporary medication quality. Particle size analysis aids in improving drug quality and improving the pharma product development process. In this research, the particle size distribution of Azithromycin oral suspension is determined using an innovative and accurate approach that was established for the purpose of determining the particle size of the suspension. This approach has produced good, repeatable outcomes. The International Conference on Harmonization's Q2 (R1) guidelines were followed in the development and validation of the wet method, which used water as the dispersant. The results showed that the method was robust and reproducible, with the percentage RSD values found within acceptance limit. The approach presented here in is a precise, verified, and efficacious technique for ascertaining the particle size distribution of oral azithromycin suspension. In-depth discussion of the particle size approach is provided to guarantee comprehension of the particle size distribution and the performance of the method across the product's lifetime.

… VAS palatability scores for each antibiotic are listed in Table II. The VAS assigned to … Cefixime was found to be significantly better tasting versus azithromycin (P < 0.036), cefprozil (P < …

… Among pediatric patients medication palatability, particularly that of oral suspensions, is essential for patient acceptance, therapeutic compliance and successful outcome …

Oral liquid medications with poor palatability may lead to non-compliance, especially among children. Often, prescribers are not aware of the palatability of the agent that they are prescribing. Eighty-six health-care professionals participated in an open-label taste test of 24 anti-infectives in stock at a pediatric teaching hospital. A sample of the product was placed on a plastic spoon and participants were asked to evaluate their overall impression based on taste, texture, smell, and aftertaste. Participants were then asked to rank the individual products on a visual analog scale. Certain anti-infective formulations were perceived as being much more palatable than others. As a follow-up study, surveys were sent out to assess the impact of the taste test. Participants were asked to evaluate their prescribing and patient counseling habits both before and after the taste test. We found that half of the volunteers had altered their prescribing and/or medication counseling habits as a result of the taste test.

… Palatability was determined using a single-blind taste test of 4 flavored antimicrobial agents. The 4 antimicrobial agents used were azithromycin… to compare palatability of antimicrobial …

Abstract Bacterial infections are still a main cause of death in children younger than 5 years, yet few age-appropriate antibiotic formulations exist, which limits treatment options and compromises quality of care. In 2023, the World Health Organization (WHO) published its first list of priority paediatric antibiotic formulations to guide research and development for age-appropriate antibiotic formulations. Both azithromycin and nitrofurantoin are on this list. Currently, no dispersible tablets are approved or available for these drugs and existing liquid forms are poorly palatable and/or contain excipients of safety concern. To support the development of age-appropriate formulations for these two antibiotics, we produced target product profiles using WHO’s methods. For azithromycin, the optimum age-appropriate formulation and dose is scored 100 mg dispersible tablets or an orodispersible 50 mg multiparticulate formulation, with dispersible 50 mg tablets as the minimum requirement. For nitrofurantoin, the optimum age-appropriate formulation is an orodispersible multiparticulate formulation or scored dispersible tablets, with dispersible tablets as the minimum requirement. Based on the WHO recommended dosage of 4 mg/kg per day for children for nitrofurantoin, the optimum unit dose is 5 mg. If scoring is feasible, a 10 mg unit dose should be developed for dosing flexibility across paediatric age groups. These profiles aim to support regulatory authorities, pharmaceutical developers, health programmes and other stakeholders in advancing safer, effective and child-appropriate antibiotic formulations.

… physicians’ opinion of the palatability of commonly prescribed pediatric liquid medications. … ing the palatability of the most common liquid medications used in children. The palatability …

The taste of medicines can significantly affect patient adherence. Pediatric patients often cannot take powder medicines because of their unpleasant taste. Therefore, patients' parents and health care professionals, including pharmacists, often combine medicines with food or beverages to make them easier for pediatric patients to consume because this can reduce their unpleasant taste. The purpose of this study was to evaluate the palatability of powder formulations of azithromycin and carbocysteine and explore their combination with food or beverages to improve palatability for pediatric patients. We quantitatively evaluated the palatability of powder formulations by performing the gustatory sensation test using the visual analog scale score. The gustatory sensation tests were performed on 16 healthy adult volunteers (age 23.0 ± 2.6 years) and indicated that some food and beverages improved the palatability of the powder formulations of azithromycin and carbocysteine. The results of this study indicate that ice cream improves the palatability of azithromycin, while yogurt improves the palatability of carbocysteine. Moreover, the subjects recommended these same combinations for pediatric patients. This study suggests that some foods and beverages improve the palatability of powder formulations, thereby decreasing the possibility that pediatric patients will refuse medications because of their unpleasant taste.

Azithromycin (AZM) is a macrolide widely prescribed in pediatrics and is characterized by low solubility and bitterness. In this study, a dual-surfactant oil-in-water (O/W) nanoemulsion …

Azithromycin is an antibiotic listed in the essential list of medicines for adults and pediatrics. Conflicting evidence has been found regarding azithromycin classification according to the Biopharmaceutics classification system (BCS). The purpose of this study was to identify the critical variables that influence the oral absorption of azithromycin in adults and pediatrics. Azithromycin solubility and dissolution studies (oral suspension) were performed in buffers and biorelevant media simulating the fasted and fed gastrointestinal tract. A PBPK model was developed for azithromycin for healthy adult volunteers and pediatrics (Simcyp® v18.2) informed by in vitro solubility and dissolution studies to predict drug performance after administration of azithromycin as an oral suspension. The developed PBPK model predicted azithromycin plasma concentrations-time profiles after administration of an oral suspension to adults and pediatrics. Sensitivity analysis of solubility vs dose suggests that absorption is independent of solubility within the therapeutic dose range in both adults and pediatrics. The developed PBPK model for adults and pediatrics was consistent with the mechanism of permeation through the intestinal membrane (passive and active processes) being the rate-limiting step of azithromycin's absorption. The physiologically based approach proposed was shown to be useful to determine the factors controlling drug absorption in adults and pediatrics.

… As mentioned in previous articles, hydrophobicity seems the key for the bitterness.In the case of azithromycin product, involved azithromycin has a comparatively large solubility in water …

Many medications including antibiotics taste bitter. The potency of these antibiotics on the 25 bitter taste receptors (T2Rs) in humans remains poorly understood. Here we characterize by sensory and structure‐function analyses how antibiotics frequently used to treat airway infections in cystic fibrosis activate multiple human T2Rs. The potency of the broad‐spectrum antibiotics, tobramycin, levofloxacin, and azithromycin on the highly expressed T2Rs in airways, T2R4, T2R14, and T2R20 was pursued. The amino acids and structural features of T2R4, T2R14, and T2R20 important for antibiotic binding were characterized by mutational analysis in heterologous cell‐based assays. Strikingly, extracellular loop 2 in T2Rs performs a key function in binding to antibiotics with contribution from residues in transmembrane helices. Our results suggest that different antibiotics activate multiple T2Rs with different potencies. An understanding of the nonantibiotic and physiologic effects mediated through T2Rs on the host cells is much needed.—Jaggupilli, A., Singh, N., De Jesus, V. C., Gounni, M. S., Dhanaraj, P., Chelikani, P. Chemosensory bitter taste receptors (T2Rs) are activated by multiple antibiotics. FASEB J. 33, 501–517 (2019). www.fasebj.org

… A dry powder suspension was developed to taste mask CPH by … Taste evaluation revealed that suspensions prepared using … with no bitter after taste [163]. An attempt was made to …

Cefuroxime axetil (CA) is an ester prodrug of cefuroxime with an unpleasant taste when administrated orally. This work was to mask the bitter taste of CA and enhance its oral bioavailability. Dry suspensions were prepared by means of wet granulation method and solid dispersion method. Binders, suspending agents and other compositions involved in the formulation were optimized. The differential scanning calorimetry (DSC) analysis indicated that CA was amorphous in the solid dispersion with stearic acid as the carrier, which contributed to an improvement of the dissolution rate. Taste evaluation was per- formed by three volunteers and taste masking was successfully achieved by the methods mentioned above. A pH 7.0 phosphate buffer was adopted to study the in vitro dissolution performance of the three formulations, i.e., two self-made dry suspensions and the com- mercial one. With a better release characteristic and a satisfying taste masking ability, the solid dispersion suspension was selected as the optimal formulation for the further pharmacokinetic study in beagle dogs. The values of Cmax and AUC0e12 for the solid dispersion suspension were about 1.78-fold and 2.17-fold higher than these of reference suspension, respectively. The obtained results demonstrated that the solid dispersion can efficiently mask the bitter taste of CA and significantly enhance its oral bioavailability. a 2013 Shenyang Pharmaceutical University. Production and hosting by Elsevier B.V. All rights reserved.

Clarithromycin (CLA) is the preferred drug for treating respiratory infections in pediatric patients, but it has the drawbacks of extreme bitterness and poor water solubility. The purpose of this study was to improve solubility and mask the extreme bitterness of CLA. We use Hot Melt Extrusion (HME) to convert CLA and Eudragit® E100 into Solid Dispersion (SD). Differential scanning calorimetry (DSC) and Powder X-ray diffraction (PXRD) were used to identify the crystalline form of the prepared SDs, which showed that the crystalline CLA was converted to an amorphous form. At the same time, an increase in dissolution rate was observed, which is one of the properties of SD. The results showed that the prepared SD significantly increased the dissolution rate of crystalline CLA. Subsequently, the SD of CLA was prepared into a dry suspension with excellent suspending properties and a taste-masking effect. The bitterness bubble chart and taste radar chart showed that the SD achieved the bitter taste masking of CLA. Principal components analysis (PCA) of the data generated by the electronic tongue showed that the bitter taste of CLA was significantly suppressed using the polymer Eudragit® E100. Subsequently, a dry suspension was prepared from the SD of CLA. In conclusion, this work illustrated the importance of HME for preparing amorphous SD of CLA, which can solve the problems of bitterness-masking and poor solubility. It is also significant for the development of compliant pediatric formulations.

The purpose of this study was to cover the bitter taste of arbidol hydrochloride (ARB) and develop dry suspension with combination of solid dispersion and flavors. Taste masking was successfully done by solid dispersion using octadecanol as the carrier by fusion method. Suspending agents, carriers and other excipients were selected. Differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR) were performed to identify the physicochemical interaction between drug and carrier, DSC analysis indicated that ARB was amorphous in the solid dispersion, FTIR spectroscopy showed no interaction between drug and carrier. Taste masking was evaluated on six volunteers with a score of 4.9. The results demonstrated successful taste masking. Water was used to study the in vitro dissolution performance of the three formulations of commercial tablet, capsule and self-made suspension. The self-made suspension showed a lower and slower release, the insoluble carrier octadecanol blocked the drug dissolving from the solid dispersion. It was indicated from the primary stability study, the self-made suspensions were sensitive to high temperature, high humidity and strong light conditions, they should be stored in sealed containers away from heat, light and humidity. © 2015 Shenyang Pharmaceutical University. Production and hosting by Elsevier B.V. All rights reserved.

… The bitter taste intensity was evaluated using volunteers by comparison of … taste masking of a bitter active like Ornidazole. The formulation development of taste masked dry suspensions …

… Hence dry suspension powder containing equivalent of 13.12 mg of PRM (equivalent to 7.5 mg primaquine base) was prepared from PRM and physical mixture. Sodium carboxy methyl …

Potassium chloride (KCl) syrup is widely used for the oral treatment of the hypokalemia. However, it is associated with unacceptable taste. In the present study, we sought to develop a palatable and easy to reconstitute KCl dry syrup as a commercially viable alternative to currently available KCl syrup. We explored the potential of Eudragit E100 as a taste-masking polymer to coat and improve the palatability of the KCl. With the help of fluid bed processor, KCl was coated with the solution containing varying amounts of Eudragit E100 (4, 6, 10 and 15%). Coating with 10% polymer solution enabled optimal fluid bed processing, higher entrapment of the KCl (81%) and better in vitro release profile in 0.1 N HCl and pH 6.8 phosphate buffer. A dry syrup formulation containing Eudragit E100 coated KCl with good physical and chemical stability in dry and reconstituted state was developed. The palatability of the optimized formulation and commercially available KCl syrup was evaluated using the Electronic Taste Sensing Machine. The developed formulation showed~ 2-fold better taste-masking compared to the commercial KCl syrup. Thus, present investigation describes the development of an effective alternative to the current KCl syrup that can offer better palatability, stability and patient compliance.

… forms such as suspensions due to a gradual loss of taste masking efficiency upon storage in … pharmaceutical granules, which can be formulated as dry syrup, suspension, conventional …

… taste of iron liquid formulations so far. However, in this study, Amberlit® IPR64 as an approved taste masking … pivoxil hydrochloride dry powder suspension. Daru. 2011;19(2):118–25. …

… taste masking by formation of inclusion complexes with cyclodextrins; taste masking by the freeze-drying process; taste masking … ) to adjust the pH of the suspension between 1.5 to 4.1.[…

… approaches include a variety of processes, such as solution layering, wet and/or dry granulation, suspension layering, alcoholic or hydroalcoholic solution layering and direct coating. …

… taste masking efficiency. ► Taste masking of suspension with Lemon and Cherry flavors. ► … Once all the solution was sprayed onto the powder bed the bed was dried until the moisture …

… saccharide tablets known as WOWTAB-DRY.In addition, new … a suspension of wicking agents using a fluidized-bed granulator known as RACTAB.Drugs with an unpleasant bitter taste …

The majority of active pharmaceutical ingredients (APIs) found in oral dosage forms have unpleasant or obnoxious taste. Taste is one of the important parameters which governs patient compliance and also decides the success of a product in the market. Undesirable taste or the bitter taste is a major challenge that formulation scientist faces with many drugs. Hence, oral administration of bitter drugs is a big challenge, especially for pediatric patients. This article focuses on various tastes masking techniques by which the characteristics of the dosage form are improved and better patient compliance can be achieved. The article also discusses various recent taste masking evaluation techniques used in oral pharmaceutical formulations. The pharmaceutical companies are now engaged in developing novel techniques to overcome the problem of taste masking by numerous patents filed for taste masking. Lists of patents for taste masking are discussed and how these patents overcome the limitations of conventional approaches of taste masking is also reviewed. The present article also emphasizes various patented platform technologies based on different techniques used for taste masking. The important features and principles involved in taste-masking approaches of various patented technologies are also discussed. A better understanding of these new patents and patented technologies will help formulation scientists to select the most suited technology for development of new products with improved taste.

… polymers provide efficient moisture protection as well as taste masking without influencing the release of the drug in … Moisture protecting and taste masking polymers used in film coating …

A variety of pharmacologically active substances, including chemotherapeutic drugs and the substances from traditional Chinese medicine (TCM), always exhibit potent bioactivities after oral administration. However, their unpleasant taste (such as bitterness) and/or odor always decrease patient compliance and thus compromise their curative efficacies in clinical application. Therefore, the developments of taste-masking techniques are of great significance in improving their organoleptic properties. However, though a variety of taste-masking techniques have been successfully used to mask the unpalatable taste of chemotherapeutic drugs, their suitability for TCM substances is relatively limited. This is mainly due to the fact that the bitter ingredients existing in multicomponent TCM systems (i.e., effective fractions, single Chinese herbs, and compound preparations) are always unclear, and thus, there is lack of tailor-made taste-masking techniques to be utilized to conceal their unpleasant taste. The relevant studies are also relatively limited. As a whole, three types of taste-masking techniques are generally applied to TCM, including (i) functional masking via sweeteners, bitter blockers, and taste modifiers; (ii) physical masking via polymer film-coating or lipid barrier systems; and (iii) biochemical masking via intermolecular interaction, β-cyclodextrin inclusion, or ion-exchange resins. This review fully summarizes the results reported in this field with the purpose of providing an informative reference for relevant readers.

… Thus, for the present work famotidine was selected as a model drug for taste masking study. … comprising of drug, cyclodextrin and hydrophilic polymer) as an approach for taste masking. …

Hot melt extrusion has gained considerable attention as a novel technique for taste masking of bitter APIs. The aim of this study was to investigate whether hot melt extrusion could be used to develop taste masked formulations of isoniazid and also to evaluate and correlate different taste assessment methods Two polymers with different physico-chemical properties, Soluplus and Eudragit E-PO were chosen as carriers for the drug. Eudragit E-PO has already been widely used for taste masking due to its selective release properties, while Soluplus has not been studied in this regard but provides a useful comparator of a polymer that should release the drug reasonably efficiently. Polymeric formulations of isoniazid were produced with drug loadings of 20% and 30% w/w. The solid state characteristics of the formulations were assessed by differential scanning calorimetry and powder X-ray diffraction. The taste of isoniazid was assessed using the rodent Brief Access Taste Aversion (BATA) model, while formulations were assessed using the electronic tongue and dissolution under simulated oral conditions. Investigation into the drug loading effect with these two polymers showed that all Soluplus based extrudates with drug loading up to 30% w/w were fully amorphous while Eudragit E-PO based extrudates contained crystalline drug as demonstrated by both DSC and PXRD, dependent on loading. BATA testing of isoniazid gave an IC50 value, i.e. the dose of drug which inhibits 50% of licks, of 11.1mg/mL. Taste assessment of the formulations using both simulated oral drug release and the electronic tongue demonstrated that Eudragit E-PO based formulations had a better taste masking efficiency than Soluplus. This is due to the fact that significantly less isoniazid is released from the Eudragit E-PO based formulations under oral conditions.

… content, in vitro taste in simulated salivary … drug in SSF was considered taste-masked and selected for formulation RDTs. The complex with drug-polymer ratio of 8:2 did not show drug …

… Therefore, taste masking methods focus on making drug completely insoluble in saliva, pH … drug taste masking is to hinder drug release in saliva, and simultaneously, to meet the drug …

… drug in the mouth to prevent or reduce interactions with taste buds [Citation13]. This article reviews polymers used for taste-masking … used to mask the taste of bitter drugs for pediatric …

… achieving rapid dissolution once the drug is ingested. … drug carriers for controlled release liquid products (4). Further, such polymers were found useful in taste protection of bitter drugs (5…

… Chitosan, Methocel E15 LV, and Eudragit E100 were used for microsphere formation, and the effect of different polymers and drug–polymer ratios on the taste masking and release …

Taste is the maximum valuable factor within the ca Taste is the maximum valuable factor within the case of orally drugs administering. Flavor covering is a prerequisite for bitter tablets to better the patient compliance, particularly in the paediatrics and geriatric population. The hassle of the sour taste of drug in pediatric formulations is a completely huge task to the formulators on this gift time. Overlaying is an effective device for the development of the sour taste of medication of patient compliance which sooner or later comes to a decision the commercial achievement of the product. In recent times, two maximum usually software are utilized to conquer the horrific flavor of the drug. The primary software consists of reduction of drug solubility within the saliva and second to modify the potential of the drug to interact with taste receptor. At present various methods are available in the market to masks the unwanted taste of the drugs. Some of them are the mass extrusion strategies and ion trade resins, molecular complexes of drugs with other chemical substances, coating of drug debris, melting method, micro encapsulation by using a formation of inclusion complexes, stable dispersions, prodrugs. USe of orally drugs administering: Flavor covering is a prerequisite for bitter tablets to better the patient compliance, particularly in the paediatrics and geriatric population. The hassle of the sour taste of drug in pediatric formulations is a completely huge task to the formulators on this gift time. Overlaying is an effective device for the development of the sour taste of medication of patient compliance which sooner or later comes to a decision the commercial achievement of the product. In recent times, two maximum usually software are utilized to conquer the horrific flavour of the drug. The primary software consists of reduction of drug solubility within the saliva and second to modify the potential of the drug to interact with taste receptor. At present various methods are available in the market to masks the unwanted taste of the drugs. Some of them are the mass extrusion strategies and ion trade resins, molecular complexes of drugs with other chemical substances, coating of drug debris, melting method, micro-encapsulation by using a formation of inclusion complexes, stable dispersions, prodrugs

… reconstituted dry suspension and studied for stability testing, according to ICH guidelines. … Based on the present research work, a stable and palatable reconstitutable dry suspension of …

… dry powders for reconstitution into oral suspensions. Once reconstituted, these oral suspensions … This study examined the stability of three frequently prescribed pediatric reconstituted …

… the most stable, the effect of different diluents on the stability of syrups, especially suspensions, … -12 and AMC-13, when prepared by separation of the dry granules before reconstitution, …

Introduction: Correct reconstitution and administration is mandatory in obtaining the adequate concentration of an antibacterial at the site of infection. Objective: The objective was to evaluate the reconstitution and administration practice adopted by a cohort of mothers in administering paediatric antibacterial suspensions. Methods: A cross-sectional descriptive study carried in Jaffna district Sri Lanka, teachers (n = 685) were selected as representative of cohort of mothers. Two-stage stratified cluster sampling technique was used; first, 4 educational zones were selected. Cluster were assigned proportionately. Antibacterial pack was given to participant to reconstitute and measure using a preferred measuring device. Questionnaire and scorecard were used. None followed all the steps of the reconstitution and administration practices correctly. Volume measured by about participants (30%) differed by over 20% than the correct volume. Conclusion: Practice of reconstitution and administration of antibacterial agents by a cohort of educated mothers was found to be unsatisfactory.