掩味 干混悬剂

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.

… 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 …

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.

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 …

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.

… 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 …

… 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. …

… 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 …

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.

… by spray congealing with lipids; taste masking by formation … ; taste masking by the freeze-drying process; taste masking by … taste of ibuprofen can be masked by making a suspension of …

… 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. …

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.

… 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 …

The majority of active pharmaceutical ingredients (APIs) found in oral dosage forms have unpleasant or obnoxious taste including, bitter, sour, salt, sweet and umami tastes. Taste is now one of the most important factors influencing the quality of the product, hence therapeutic value, compliance, and acceptance of the patient. Masking the unpleasant taste of active pharmaceutical ingredients (APIs) is a major challenge in the pharmaceutical oral dosage form design and in the development of such oral dosage forms, especially those used for pediatric patients. The desire of improved palatability in these products has prompted the development of numerous formulations with improved performance and acceptability. This reason is an initiative for the development of various taste masking technologies by which the characteristics of the dosage form is improved and good patient compliance is achieved. The present article reviews the earlier applications and methodologies of taste masking and discusses the most recent developments and approaches of bitterness reduction and to give an idea about the traditional and recent taste masking evaluation techniques whereby, increasing palatability for oral pharmaceuticals.

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.

… The best way to achieve taste masking was to first administer CAMD mixed with chocolate jelly, … The chocolate jelly will be useful for taste masking of bitter macrolide drug formulations, …

… It was concluded the appropriate choice of jelly with the right pH is essential for taste masking. Suitable jellies might be used to improve patient compliance, especially in children. The …

Regulations in the US and EU require and incentivize the development of palatable, age-appropriate medicines for children. However, the taste masking challenge of new drug actives is generally unknown, making development of palatable drug products extremely difficult. To develop palatable drug products, formulation scientists first need to determine if the drug active is bitter, has an offensive aroma (malodor) or is burning as each perception requires a different formulation approach. This retrospective compilation of results of 155 taste assessment studies reveals diversity in aversive flavor attributes of active ingredients. Bitterness was the primary taste masking challenge for 65% of the drug actives. Aversive aromas (e.g., solvent, fishy, oxidized oil) were the second most common challenge, impacting 8% of drug actives. Approximately 5% had trigeminal irritation, and a smaller subset were sour or salty (4%). None were found to be sweet. Of note, 14% of drug actives were “bland” in flavor, with no measured aversive attributes. Complicating development, most actives (>90%) were found to have multiple aversive flavor attributes. These findings highlight the need to determine the aversive attributes early in clinical development (Phase 1) to guide dosage form selection and formulation design.

Many approved oral paediatric medicines continue to have poor taste acceptance, suggesting that the ingredient blends employed in these medicines are not adequately effective in taste-masking drugs with strongly aversive tastes. To address this inadequacy, this narrative review provides a comparative evaluation of taste-masking ingredients used by the pharmaceutical industry with those employed in the food industry, as well as food items used by caregivers to mask the unpalatable taste of medicines for young children. Information was sourced from academic databases, industry publications, and caregiver forums on informal social platforms. Ingredients were classified into sweeteners, salts, acids, fats, peptides/amino acids, flavourants, cyclodextrins and polymers, with their taste-masking mechanisms delineated into receptor-level interactions and the creation of physical barriers and alternative dominant taste. Their applications are compared across the regulated medicinal and consumer food products, and in home remedies. Sweeteners show the highest cross-domain convergence as they are used in medicinal and food products and are recommended by caregivers. Peptides, amino acids, salt and texture modifiers applied in food and home remedies may have translational potential in medicines. Challenges, including drug–food interactions, regulatory constraints, and the need for combination approaches, are addressed. A decision framework is also designed to guide the development of simple, acceptable, and effective ingredient-based taste-masking systems for drugs with aversive tastes.

It is well-known that plenty of active pharmaceutical ingredients (API) inherently possess an unpleasant taste, which influences the acceptance of patients, especially children. Therefore, manufacturing taste-masked dosage forms has attracted a lot of attention. This review describes in detail the taste-masking technologies based on the difference in the taste transmission mechanism which is currently available. In particular, the review highlights the application of various methods, with a special focus on how to screen the appropriate masking technology according to the properties of API. Subsequently, we overviewed how to assess taste-masking efficacy, guiding researchers to rationally design taste-masking formulations. Graphical Abstract

The development of oral pediatric forms by pharmaceutical companies is still insufficient. In fact, many drugs used in paediatric oncology, such as temozolomide, are not labeled and adapted for paediatric use. Temozolomide (TMZ) is an alkylating agent used as the standard of care for many adult and pediatric brain tumours, such as neuroblastoma, glioblastoma and medulloblastoma. The present study was carried out to propose a suitable and palatable formulation of the oral liquid preparation of TMZ. The suspension is composed of TMZ suspended in SyrSpend SF pH 4, as well as TMZ crystallization stabilizing agents and sweetening agents. To reach this formulation, several taste-masking agents were evaluated. Here, we describe the method of preparation of the formation as well as the monocentric population treated with the formulation over a 5–year period. A 20 mg/mL TMZ suspension was developed. TMZ suspension is stable for 6 weeks, stored between 2 and 8 degrees, protected from light, and compatible with nasogastric tubes. Thirty-eight patients participated in the palatability study and choose cola flavour, and 104 patients were treated in Gustave Roussy with the developed suspension; no unexpected event was reported. To conclude, we propose here a new TMZ liquid formulation which is stable for at least 6 weeks and well-tolerated with extensive feedback.

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

Orodispersible dosage forms, characterized as quick dissolving and swallowing without water, have recently gained great attention from the pharmaceutical industry, as these forms can satisfy the needs of children, the elderly, and patients suffering from mental illnesses. However, poor taste by thorough exposure of the drugs' dissolution in the oral cavity hinders the effectiveness of the orodispersible dosage forms. To bridge this gap, we put forward three taste-masking strategies with respect to the intensity of time, concentration, and perception. We further investigated the raw material processing, the composition of auxiliary material, formulation techniques, and process control in each strategy and drew conclusions about their effects on taste masking.

… taste masking and comparison of taste intensity during formulation development using a multichannel taste … the active pharmaceutical ingredients in oral liquid or suspension formulation…

… The solvent is removed from a frozen drug solution or a frozen drug suspension containing … to mask the bitter-tasting drug. The combination of lyophilisation and taste masking creates a …

… out on drug palatability evaluation based on electronic … various dosage forms, including dry suspensions, oral solutions, … system, to comprehensively evaluate the palatability and in vitro …

… Based on the present research work, a stable and palatable reconstitutable dry suspension of ARM is proposed in pediatrics as an alternative to capsule and can be used as flexible …

… palatability of CAMDS, while the uniformity of drug loading also seems to be important, as dry … the significant taste masking effect for dry syrup suspension was well demonstrated in our …

… In conclusion, a palatable suspension of the bittertasting neuroleptic compound, remoxipride, was developed based on microcapsules dispersed in an oily vehicle. Largescale …

… The suspensions were agitated with stirrer bar … suspensions were evaluated in human gustatory sensation tests. The intensities of sweetness, sourness and saltiness13) were evaluated …

… Liquid formulations exist in various dosage forms such as suspensions, solutions, and emulsions. Three studies included in this review investigated the effect of liquid formulations on …

Palatability is a critical determinant of acceptability and adherence for oral drug products, especially in pediatric and geriatric populations, yet its evaluation remains fragmented across dosage forms and often disconnected from formulation-development decisions. In this review, we propose Palatability-by-Design (PbD) as a unified framework that treats palatability not as a loosely defined sensory outcome, but as a development variable with identifiable failure modes, measurable sensory critical quality attributes (CQAs), and controllable formulation/process levers. We first define a two-dimensional framework comprising swallowability (oral physical comfort) and palatability (sensory appreciation), and then outline major sensory failure modes that are relevant to oral drug development. Next, we compare subjective and objective evaluation methods using a fit-for-purpose logic, emphasizing decision relevance, surrogate calibration, and the need to anchor instrumental readouts to perception-relevant endpoints. We further integrate these elements into a PbD workflow that links sensory CQAs to risk assessment, formulation/process variables, acceptance criteria, and verification. Finally, we summarize failure-mode-guided optimization strategies, including taste masking and dosage-form modification, and discuss future needs for data standardization, translational calibration, and patient-centred implementation. By aligning sensory science with pharmaceutical quality and control logic, PbD provides a more practical basis for rational, patient-focused oral product development.

… data related to palatability. However, based on results of this review, palatability is often … Limited evidence regarding a correlation between palatability and treatment adherence in …

… an undesirable taste9. For this reason, a secondary method for taste masking in addition to … In this study, we attempted to formulate clindamycin–resin complex into an oral suspension …

Abstract In the present work, an attempt has been made to mask the bitter taste of Levetiracetam using various ion-exchange resins such as Amberlite IRP69 and Duolite AP143. The physicochemical characteristics of the drug–resin complex in the solid state were studied. FT-IR studies revealed that there is no interaction between drug and resin. The DSC and XRD studies proved that the drug is in amorphous nature. Using the same concentration of resins, Xanthan gum as suspending agent in a liquid dosage form for pediatric use was formulated. Evaluation parameters such as drug content, sedimentation volume, re-dispersibility and viscosity of the prepared suspension were found to be satisfactory. The higher Zeta potential value indicates the stability of the suspension. Suspension prepared with Duolite AP 143 efficiently masks the bitter taste of Levetiracetam compared to Amberlite IRP69. From the in vitro drug release, a formulation with 1:2 ratios of resin has shown the maximum release at the end of 90 minutes. The sustained effect is due to one of the properties of the resin. The release profile follows zero order kinetics. The results obtained in this work show that drug–resin complexes effectively masked the bitter taste of Levetiracetam while liquid formulation provides an easier way to administer and to overcome problems with noncompliance of pediatrics.

Abstract The aim of the study was to taste mask ciprofloxacin (CP) by using ion-exchange resins (IERs) followed by sustain release of CP by forming interpenetrating polymer network (IPN). IERs based on the copolymerization of acrylic acid with different cross linking agents were synthesised. Drug-resin complexes (DRCs) with three different ratios of drug to IERs (1:1, 1:2, 1:4) were prepared & evaluated for taste masking by following in vivo and in vitro methods. Human volunteers graded ADC 1:4, acrylic acid-divinyl benzene (ADC-3) resin as tasteless. Characterization studies such as FTIR, SEM, DSC, P-XRD differentiated ADC 1:4, from physical mixture (PM 1:4) and confirmed the formation of complex. In vitro drug release of ADC 1:4 showed complete release of CP within 60 min at simulated gastric fluid (SGF) i.e. pH 1.2. IPN beads were prepared with ADC 1:4 by using sodium alginate (AL) and sodium alginate-chitosan (AL-CS) for sustain release of CP at SGF pH and followed by simulated intestinal fluid (SIF i.e. pH 7.4). FTIR spectra confirmed the formation of IPN beads. The release of CP was sustain at SGF pH ( 75%). The kinetic model of IPN beads showed the release of CP was non-Fickian diffusion type.

Atomoxetine hydrochloride (ATH) is a first-line medication used to treat Attention Deficit Hyperactivity Disorder (ADHD) in children. However, it poses challenges such as a bitter taste and difficulties in dose adjustment. While once-daily administration may result in excessive drug exposure, twice-daily dosing improves plasma drug concentration stability but can reduce patient compliance, especially in school-aged children. To address these challenges, a novel strategy was proposed that involves encapsulating ATH into ion exchange resins (IERs) (referred to as ATH@IER). The pH-responsive release of ATH from the ATH@IER exhibited a limited release rate in neutral conditions, effectively masking the bitter taste, which was evaluated through electronic tongue analysis. The cation-responsive release of ATH from the ATH@IER demonstrated immediate-release (IR) property, which was combined with Eudragit® RS100 coated ATH@IER (ATH@MC) to establish a biphasic release system. ATH orally disintegrating tablets (ATH ODT) were manufactured using a composition of ATH@IER and ATH@MC (40:60, w/w), along with other excipients. Pharmacokinetic studies demonstrated that a single dose of ATH ODT produced a bimodal plasma concentration, resulting in a two-fold decrease in peak concentration (Cmax) while maintaining an unchanged area under the drug concentration–time curve (AUC0-t) compared to the commercial ATH oral solution administered once. Notably, the plasma drug concentration of ATH ODT remained steadier than that of the commercial product when administered twice. In conclusion, ATH ODT represents a promising formulation that effectively masks bitter taste and provides biphasic release for the treatment of ADHD.

… The ion exchange mechanism was the prime cause of drug release. By virtue of ion exchange resins, the benefits achieved of taste masking … liquid suspensions based on ion- exchange …

The purpose of this research was to mask the intensely bitter taste of Chloroquine phosphate using ion exchange resin and to formulate oral suspension of the taste masked drug. Batch method was used for formation of drug resin complex. Various ion exchange resins such as Doshion P 544 S and Kyron T- 114 were tried to obtained taste masked drug resin complex (DRC). Optimization of drug loading was carried out. With Doshion P 544 S, the drug-resin proportion of 1:4 achieved equilibrium in 5 hours. 96% w/w of drug loading was possible by this method. Complex formation was confirmed by DSC and IR studies. Oral taste masked suspension was prepared using xanthum gum at various concentrations 0.1%, 0.2% and 0.4% respectively. CPR 1 and CPR 2 batches showed satisfactory assay result that is it fulfills the official requirements. But physical properties of suspension were not satisfactory. CPR 1 was not easily redispersible and with CPR 2 caking was observed with sedimentation volume of 0.4, hence these batches were rejected. CPR 3 was found to be optimized batch as it showed complied assay results were found to be easily redispersible even after 7 days with no cake formation and sedimentation volume of 0.98. and was evaluated for various parameters such as Colour, pH, Viscosity etc. Thus, successful taste masking and formulation of suspension with taste masked drug especially for pediatric, geriatric, and non cooperative patients.

Graphical abstract Figure. No caption available. ABSTRACT Taste masking is important for some unpleasant tasting bioactives in oral dosage forms. Among many methods available for taste‐masking, use of ion‐exchange resin (IER) holds promise. IER combined with hot melt extrusion (HME) may offer additional advantages over solvent methods. IER provides taste masking by complexing with the drug ions and preventing drug dissolution in the mouth. Drug‐IER complexation approaches described in literatures are mainly based either on batch processing or column eluting. These methods of drug‐IER complexation have obvious limitations such as high solvent volume requirements, multiprocessing steps and extended processing time. Thus, the objective of this study was to develop a single‐step, solvent‐free, continuous HME process for complexation of drug‐IER. The screening study evaluated drug to IER ratio, types of IER and drug complexation methods. In the screening study, a potassium salt of a weakly acidic carboxylate‐based cationic IER was found suitable for the HME method. Thereafter, optimization study was conducted by varying HME process parameters such as screw speed, extrusion temperature and drug to IER ratio. It was observed that extrusion temperature and drug to IER ratio are imperative in drug‐IER complexation through HME. In summary, this study has established the feasibility of a continuous complexation method for drug to IER using HME for taste masking.

… When loaded on ion-exchange resins, potential topical drug can be delivered to the body and fundus of the stomach, where colonies of H. pylori are known to exist, or site-specific drug …

Abstract Doxilamine orodispersible tablets were developed with considerable increase in drug release as compared to marketed formulations, seven formulations were developed and studied. The difference in drug release values was found to be 100.45 ± 1.89 and 56.47 ± 1.89, respectively. To prevent bitter taste and unacceptable odour of the drug, the drug was taste masked with weak cation exchange resins like Indion 234, Indion 204 and Indion 414. The drug was characterized according to different compendial methods, on the basis of identification by UV spectroscopy, pH, organoleptic properties and other tests. Among the three resins, one was selected for further studies i.e., Indion 234, because of high drug loading capacity. Drug–resin complex was prepared using batch method and effect of various processing parameters viz. drug–resin ratio, pH, temperature and drug concentration was studied to optimize the loading conditions. Maximum loading was obtained at drug–resin ratio 1:2, pH 5, temperature 50 °C and drug concentration 4 mg/ml. A successful taste masking of resinate was confirmed by time intensity method and also by taking drug release in 0.01 N hydrochloric acid and in simulated salivary fluid. The values of pre-compression parameters evaluated, were within prescribed limits and indicated good free flowing properties. The data obtained of post-compression parameters such as weight variation, hardness, friability, wetting time, water absorption ratio, content uniformity, disintegration time and dissolution and was found superior over conventional formulation. The F5 batch with disintegration time 25.24 ± 0.75 and dissolution 100.46% ± 3.78 was selected as optimized formulation. This was compared with conventional marketed formulation and was found superior. Batch F5 was also subjected to stability studies for three months and was tested for its disintegration time, drug contents and dissolution behaviour monthly. It was observed that the contents of the tablets remained the same. By an appropriate selection and combination of excipients it was possible to obtain orodispersible and taste masked tablets.

… Over the succeeding five decades, ion-exchange resins … ie, excipients), taste masking of bitter tasting drugs, controlled and … release performance of various suspension formulations was …

The aim of this study was the development of griseofulvin (GRI) loaded β-cyclodextrin (β–CD) based nanosponges for bitter taste masking, improving dissolution rate and oral bioavailability. Plain NS (NS1 NS2 and NS3) were fabricated by reacting β-CD with the cross-linker diphenyl carbonate at different molar ratios (1:2, 1:4 and 1:6, respectively) using ultrasonication method. The NS2 provided both highest %yield and GRI solubilization enhancement. Thus, the drug was loaded in NS2 at different NS2: drug weight ratios in presence or absence of 0.25%w/w polyvinylpyrolidone (PVP k30). The GRI loaded NS (F1) that provided highest drug loading capacity and entrapment efficiency (47.20 ± 0.38%, 84.91 ± 0.30%, respectively) was morphologically examined using scanning electron microscopy (SEM). Also, Particle size, zeta potential, differential scanning calorimetry (DSC), Fourier transform infra-red (FT-IR), nuclear magnetic resonance (NMR) spectroscopy, in-vitro release, taste masking potential were evaluated. Moreover, in-vivo Pharmacokinetic studies were performed on rats. The F1 showed particle size 665.9 ± 13.8 nm and zeta potential −21.5 ± 0.7 mV. The DSC and FT-IR analysis confirmed the complexation of GRI with NS2. Nanosponges (F1) provided 3.19, folds increase in dissolution efficiency %, 2.13 and 3.78 folds increase in Cmax and AUC0-48 compared to plain GRI. Taste masking evaluation confirmed the potential of GRI nanosponges (F1) in masking the bitter taste of GRI completely. The study confirmed that complexation of GRI with NS would be a viable approach for masking the bitter taste of GRI and improving oral bioavailability, that Cmax, Tmax and AUC 0–48 were significantly higher for the developed formulation (F1).

… solution by crystallization or by freeze-drying. Company ‘B’ stirred the aqueous suspension of cetirizine 2HCl and βCD for 30 min, dried, pelleted and compressed the formulation to …

… to mask fluconazole (FLU) taste and improve its rheological properties by an efficient process of cyclodextrin … with cyclodextrins in solid-phase use drying techniques such as spray-…

One of the important parameters in the case of dosage form is taste. Most of the drugs available in oral dosage form have an unpleasant taste which leads to patient incompliance and affects the success ratio of products in market. Geriatric and paediatric patients suffer more with a bitter taste of medicines. According to the studies reported, it is found that 50% of the population have problem of swallowing tablets, especially the pediatric and geriatric population. Masking the taste of bitter drugs has become necessary in the pharmaceutical field and increasing interest of researchers to develop various methods for masking the bitter taste of drugs. Five major tastes that are felt by our tongue are salt, sour, sweet, bitter and umami. When the drug dissolves with saliva, drug molecules interact with taste receptors present on the tongue and give taste sensations. Although many solid oral dosage forms like pills, tablets have additional advantage of masking and encapsulation of bitter taste drugs but they might not be effective for children because they may or may not swallow pills or tablets. There are various other methods that masks the bitter taste of drugs such as addition of sweeteners and flavouring agents, granulation, coating, inclusion complexes, extrusion method, ion-exchange resins etc, discussed in first section of article. The second part of this article consists of various nanotechnology-based drug delivery systems that were fabricated by researchers to mask the bitter taste of drugs. A brief of recent literature on various nanocarriers that were fabricated or developed for taste masking has been discussed in this part. A better understanding of these methods will help researchers and pharmaceutical industries to develop novel drug delivery systems with improved taste masking properties.

… Use of cyclodextrins as taste masking agent is widely reported (… CDs (especially β-cyclodextrins) for taste masking is generally … suspension obtained was then subjected to freeze drying …

Oral lyophilisates are one of the orodispersible tablets produced by lyophilization technique. Due to their porous structure, they instantly disintegrate when contacting saliva. Generally, they are suitable for drugs with a short onset of action, such as nonsteroidal anti-inflammatory drugs (NSAIDs). Therefore, formulations of piroxicam lyophilisates and their properties were investigated. Because piroxicam is classified as a low solubility but high permeability drug, a solubility enhancing agent should be included in the formulation. The influence of β-cyclodextrin (βCD) and hydroxypropyl-β-cyclodextrin (HPβCD) on disintegration time and morphology of piroxicam lyophilisates was studied. Furthermore, the satisfactory taste-masking efficiency of HPβCD in piroxicam lyophilisates was studied by sensory test. The effect of matrix polymer mixtures on disintegration time was previously evaluated. The appropriate ratio of polymer mixture, i.e., gelatin and hydroxypropyl methylcellulose (HPMC), provided lyophilisates with the fastest disintegration time (<30 s) was designated for further studies. The presence of both CDs decreased disintegration time and modified the surface and matrix of lyophilisates. With the theoretical study based on molecular mechanics methods and the investigation through the chemical shift of protons using nuclear magnetic resonance (NMR), piroxicam formed inclusion complexes with both βCD and HPβCD. Dissolution profiles of piroxicam/HPβCD lyophilisates revealed improved piroxicam solubility by inclusion complex formation. Finally, the piroxicam/HPβCD lyophilisates demonstrate the bitterness suppression in healthy volunteers.

… suspensions. Further, complexation by complexing agents like … the α-cyclodextrin cavity could not serve for complexation of the whole molecule and also taste masking by γ-cyclodextrin …

Abstract In drug formulation development cyclodextrins (CD) are well known for their ability to complex hydrophobic compounds. They are widely used to enhance the solubility of an active pharmaceutical ingredient (API) with the benefit of masking a possible unpleasant taste. Maltodextrins (dextrose equivalent: MD1–17 and MD2–13) with a high amylose content have very similar molecular properties but are mainly used for nutritional supply. This study compared the solubilizing and taste-masking capacities of two new MD grades to well-established water-soluble CD. We used two poorly soluble APIs, dextromethorphan hydrobromide and loperamide hydrochloride, to compare the effects of CD and MD on solubility. The addition of either 5 mM CD or MD to an oversaturated API solution increased solubility of both dextromethorphan hydrobromide (CD: +9.77%, MD1: +19.55%, MD2: +24.40%) and loperamide hydrochloride (CD: +47.43%, MD1: +75.34%, MD2: +112.27%). These APIs are described as being of bitter taste. The taste-masking effects of CD and MDs on dextromethorphan HBr, loperamide HCl and the highly soluble cetirizine HCl were evaluated through electronic taste sensing systems (e-tongues). These systems based on potentiometric mechanism are equipped with different types of sensor membranes to distinguish between different taste attributes of investigated samples. Bitterness sensor results were analyzed with principal component analysis, which allows a relative scoring of API complexes. The analysis revealed better masking capability of CD for cetirizine HCl (CD  These results indicate a better effect of MDs on solubility compared to CD for all tested APIs and possible better taste-masking properties of MDs compared to CD for some APIs. We conclude that the use of MDs presents a promising new approach for developing drug formulations.

… that taste mas ing of drugs with cyclodextrins can be improved when a molar excess of dissolved cyclodextrin … oral solutions, suspensions and tablets of various bitter drugs to overcome …

… Spray drying is a method where a drug solution/suspension is sprayed into a hot air stream, producing … 2-Hydroxypropylβ-cyclodextrin Investigating the effect of cyclodextrin on taste …

… This drug is now marketed as a film-coated tablet (Elen 20 mg tablet). However, IDX is … develop taste-masked powders of IDX without lowering bioavailability by coating microparticles of …

… In the present research, the proposed double-coated taste-masking microparticles of ENRO (DTME) were prepared and the obtained DTME were characterized in terms of their …

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.

… for taste masking based on multiparticulates coated with Kollicoat VR Smartseal 30D formulated as liquid oral suspensions. Coating … Coated microparticles could be used for single dose …

Abstract Taste of a pharmaceutical formulation is an important parameter for the effectiveness of pharmacotherapy. Cetirizine dihydrochloride (CET) is a second-generation antihistamine that is commonly administered in allergy treatment. CET is characterized by extremely bitter taste and it is a great challenge to successfully mask its taste; therefore the goal of this work was to formulate and characterize the microparticles obtained by the spray drying method with CET and poly(butyl methacrylate-co-(2-dimethylaminoethyl) methacrylate-co-methyl methacrylate 1:2:1 copolymer (Eudragit E PO) as a barrier coating. Assessment of taste masking by the electronic tongue has revealed that designed formulations created an effective taste masking barrier. Taste masking effect was also confirmed by the in vivo model and the in vitro release profile of CET. Obtained data have shown that microparticles with a drug/polymer ratio (0.5:1) are promising CET carriers with efficient taste masking potential and might be further used in designing orodispersible dosage forms with CET.

… Masking of the unpleasant taste of a drug improves compliance and product value. Various taste masking techniques such as capsule ®lling or coating … were used for taste masking of a …

… ® , is a film-coated tablet. Tablet coating is popularly used to mask unpleasant tastes, but is not … The objectives of this study were to design and optimize a taste masked microparticulate …

… Consequently, the aim of taste masking microparticles … be carried out using polymeric coating processes in fluid bed … -bed coating approach, Stange formulated the bitter taste masking …

Lacosamide (LCM) is a third-generation antiepileptic drug. Selective action of the drug on voltage-gated sodium channels reduces side effects. Oral administration of LCM shows good pharmacokinetic profile. However, the bitter taste of LCM is a barrier to the development of oral formulations. In this study, we aimed to prepare encapsulated LCM microparticles (MPs) for masking its bitter taste. Encapsulated LCM MPs were prepared with Eudragit® E100 (E100), a pH-dependent polymer, by spray drying. Three formulations comprising different ratios of LCM and E100 (3:1, 1:1, and 1:3) were prepared. Physicochemical tests showed that LCM was in an amorphous state in the prepared formulations, and they were not miscible. LCM-E100 (1:3) had a rough surface due to surface enrichment of LCM. Increased E100 ratio in LCM-E100 MPs resulted in better taste-making effectiveness: LCM-E100 (1:1) and LCM-E100 (1:3) showed good taste-masking effectiveness, while LCM-E100 (3:1) could not mask the bitter taste of LCM. Dissolution results of the prepared formulations showed good correlation with taste-masking effectiveness. Nevertheless, high E100 ratio reduced the stability of the prepared formulations. Especially the difference in initial dissolution profile observed for LCM-E100 (1:3) indicated rapid reduction in taste-masking effectiveness and surface recrystallization. Therefore, LCM-E100 formulation in the ratio of 1:1 was selected as the best formulation with good taste-masking effectiveness and stability.

… Moreover, the coatings and the granulation of the active ingredient … taste masking by creating a physical barrier to protect the bitter drugs from coming in contact with the patients’ taste …

Microencapsulation is one of the most commonly used taste masking techniques. It can be accomplished by various methods, including coacervation, solvent evaporation, extrusion and spray-drying. Enalapril maleate, a bitter-tasting ACE-inhibitor, is available worldwide in conventional tablet formulations and as oral solution in the USA. The purpose of this study was to develop enalapril-loaded microparticles using spray-drying and to test their taste masking potential. Eudragit EPO® was used as a taste masking polymer for the preparation of a drugpolymer suspension. The suspension was then spray-dried under the following conditions: inlet temperature 65 °C, outlet temperature 30 °C, aspiration 100% and pump rate 10%. The drug-to-polymer ratio was varied and seven different microparticle models were developed. The yield of spray-dried particles ranged from of 51.3 to 85.4%, drug loading varied from 7.75 to 24.69% and encapsulation efficiency ranged from 58.5 to 95.7%. The particle size varied between 5.00 μm and 17.47 μm and the moisture content varied between 7.1% and 10.3%. In vitro taste assessment revealed minimal or no ENA release in artificial saliva. In vivo studies (with experimental animals and healthy volunteers) were used to evaluate the taste masking potential of spray-dried microparticles of enalapril maleate and Eudragit EPO®.

The objective of this research was to optimize the tasted-masked microparticles for orally disintegrating tablets containing donepezil hydrochloride using quality risk assessment and design of experiment approaches. The double emulsion solvent evaporation technique using aminoalkyl methacrylate copolymer (AMC) was used to prepare taste-masked microparticles. Factors affecting the quality of the taste-masked microparticles were analyzed using an Ishikawa diagram. A risk-ranking approach was used to rank the formulation and process risks. Furthermore, the effect of AMC quantity, stirring time, and volume of outer water phase on various responses, such as particle size, the amount of drug dissolved at 5 min (Q5) in simulated saliva fluid, and mean dissolution time (MDT) in simulated gastric fluid, was investigated using the Box-Behnken design. The optimized microparticles were then used to prepare orally disintegrating tablets (ODTs) and evaluated by in vitro and in vivo testing. The results demonstrated that particle size was influenced by the AMC amount and stirring time. Q5 was significantly affected by the amount of AMC and the volume of the outer water phase. On the other hand, these two factors had a positive effect on MDT. The optimized microparticles had a particle size of 174.45 ± 18.19 µm, Q5 of 5.04%, and MDT of 5.97 min. The ODTs with taste-masked microparticles showed acceptable in vitro dissolution with an MDT of 5 min. According to the results of a panel of six human volunteers, they greatly improved palatability.

Oral suspension is the most preferred dosage form for the paediatric population because of the difficulties related to solid medications, such as the swallowing limitations, bitter taste, and poor oral bioavailability, which can cause serious impairment to attain a successful treatment. Given the importance of successful therapies, there is a need for safe and effective commercially-available paediatric oral suspension and their characterization. For the latter, it is important to identify safe excipients and preservatives. The paediatric group is a diverse category which includes infants and teenagers, with major pharmacokinetics and pharmacodynamics differences, mainly because of physiological and behavioral variations. Therefore, finding a single formulation for paediatric population remains a challenge, as well asthe formulation of stable-in-time suspension. In addition, drug's dissolving characteristic and permeation, are the main determinants for oral absorption, which are closely related to drug release kinetics from the pharmaceutical form. In this context, drug release profile is an important and limiting step in oral bioavailability, particularly for BCS class II drugs; thus, it is possible to increase bioavailability and minimize adverse effects by changing the release rate of such drugs. This review covers all the aspects for paediatric oral suspension development, and analyses the considerations for excipients selection as a crucial task for effectively choosing a safe and effective pharmaceutical form and correctly dosing paediatric patients.

Norvir® (ritonavir) is a Biopharmaceutical Classification System Class IV compound with poor solubility in water (~5 µg/mL) and limited oral bioavailability. Early stage development efforts were focused on an oral solution (OS) which provided reasonable bioavailability but exhibited taste-masking challenges and required the use of solvents with potential pediatric toxicity. Norvir® oral powder, 100 mg (NOP) was developed to replace OS. The objective of this study is to provide an overview of the development of NOP and palatability assessment strategy. Palatability of NOP was assessed using the flavor profile method: (1) As an aqueous suspension dose/response and (2) evaluation with foods. The dose/response sensory analysis indicated that NOP has strong intensity bitterness and burnt aromatics (3 on the 0–3 flavor profile scale) at the clinical dose (100 mg/10 mL) and the recognition threshold was determined to be 0.3 mg/10 mL. To improve palatability, 100 mg/10 mL NOP aqueous suspension was evaluated with foods. Consuming foods high in fat and/or sugar content after NOP administration successfully reduced bitterness to a 1.5 intensity. In summary, NOP provides dose flexibility, enhanced stability, eliminated solvents, and maintains consistent bioavailability, with reduced bitterness and improved palatability via administration with common food products.

… The objective of this study was to evaluate the palatability of four commonly … palatability of antibiotics, which have been conducted in adults, this study was conducted in pediatric …

The administration of medications to children has been a challenge for parents and caregivers for generations. Pharmaceutical companies have often overcome the difficulties of weight-based dosing and the -inability of most young children to swallow solid dosage forms by creating oral liquids. While oral liquids -offer advantages in terms of dose flexibility, swallowability, and ease of administration for young children and patients with enteral tubes, they have been plagued by issues such as taste, volume, and texture, to name a few. While the recommendations for broader use of oral syringes can help with the issue of measuring accuracy and incremental dosing, the issues of poor taste and frequently unacceptable volumes for doses remain a problem. New oral dosage forms which have begun to enter the United States marketplace have the potential to improve adherence and acceptability of oral medications for children, but come with their own unique challenges.

… Suspension formulations should be considered when solubility cannot be modulated. By minimizing drug in solution form, suspensions improve palatability and allow increased drug …

The aim of this review was to map the currently available evidence on acceptability of oral paediatric medicines to aid in the selection of suitable platform formulations for the development of new acceptable paediatric products.

… the poor palatability of the buffered tablets. Therefore, we believe that administration of pediatric … In conclusion, health care professionals should consider the use of didanosine pediatric …

… most palatable oral antibiotic suspensions. Currently loracarbef is available in oral capsule and suspension … pharmacokinetic investigation of the oral suspension in pediatric subjects. …

The acceptability of pediatric pharmaceutical products to patients and their caregivers can have a profound impact on the resulting therapeutic outcome. However, existing methodology and approaches used for acceptability assessments for pediatric products is fragmented, making robust and consistent product evaluations difficult. A pediatric formulation development workshop took place in Washington, DC in June 2016 through the University of Maryland's Center of Excellence in Regulatory Science and Innovation (M-CERSI). A session at the workshop was dedicated to acceptability assessments and focused on two major elements that affect the overall acceptability of oral medicines, namely swallowability and palatability. The session started with presentations to provide an overview of literature, background and current state on swallowability and palatability assessments. Five parallel breakout discussions followed the presentations on each element, focusing on three overarching themes, risk-based approaches, methodology and product factors. This article reports the key outcomes of the workshop related to swallowability and palatability assessments.

… basis for a pharmaceutical palatability model that connects … a predictive model for pediatric liquid palatability that uses … The model is not intended to replace pediatric acceptability …

… and assess palatability in pediatric oral solid dosage forms. … on recommended dosage forms for pediatric patients—based … oral dosage forms or issues of palatability and swallowability. …