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Taste masking techniques for bitter drugs-an overview
Abstract
Taste is mainly a function of taste buds in the mouth. In the formulation for pediatric & geriatric, bed ridden & non-cooperative patients the main challenge to the compounding pharmacist is to mask the taste of obnoxious and bitter drugs, result is patient not receiving the optimal therapeutic value of their medication. Taste masking is the main factor in the development of the dosage form. It opens the doors for new inventions and patents. Many techniques have been developed which not only improve the taste of molecule but also the formulation and performance of the molecule. The main objective of present review is to explore different method, technologies and evaluations to mask the obnoxious taste of drugs, so that patients can use these drugs without hesitation of taste.
... Polega na powlekaniu gorzkich cząsteczek API polimerami hydrofilowymi lub hydrofobowymi, lub ich mieszaniną, dzięki czemu możliwe jest skuteczne zamaskowanie ich nieprzyjemnego smaku [15]. Rozmiar mikrokapsułek zazwyczaj waha się w granicach od 1 do 1000 µm, natomiast nanokapsułek od 1 do 1000 nm. ...
... Polimerami wykorzystywanymi podczas mikroenkapsulacji są m.in. karboksymetyloceluloza sodowa, żelatyna, etyloceluloza, alkohol poliwinylowy i octanoftalan celulozy [8,15]. W przypadku maskowania smaku najczęściej wykorzystywanym polimerem jest Eudragit E [3]. ...
... Mikroenkapsulacja znalazła zastosowanie podczas maskowania takich substancji czynnych, jak np. difosforan chlorochiny, difenhydramina, aksetyl cefuroksymu, klarytromycyna oraz ibuprofen [15,19]. ...
Nieprzyjemny smak, którym charakteryzuje się liczna grupa substancji leczniczych może stanowić wyzwanie zarówno dla naukowców na etapie projektowania określonej postaci leku, jak również dla pacjenta podczas przyjmowania danego preparatu. Wrażenia smakowe pełnią istotną rolę w dzisiejszych czasach, będąc niekiedy jednym z kryteriów wyboru, którym kieruje się pacjent podczas wizyty w aptece ogólnodostępnej oraz mogą one wpływać na pozytywny odbiór preparatu i w efekcie udaną komercjalizację produktu leczniczego. Doznania smakowe pełnią kluczową rolę w przypadku doustnych postaci leku, a przede wszystkim rozpuszczalnych postaci oraz pozostałych płynnych form leków. Główną grupą docelową płynnych preparatów leczniczych są pacjenci pediatryczni oraz osoby mające problem z połykaniem stałych doustnych postaci leku, a także seniorzy. Zwłaszcza dzieci stanowią grupę pacjentów, dla których walory smakowe są niezwykle istotne. Substancje lecznicze charakteryzujące się nieprzyjemnym smakiem i/lub zapachem, poprzez niską akceptację ze strony pacjenta mogą także oddziaływać na zmniejszenie skuteczności procesu leczenia. Skuteczne zamaskowanie nieprzyjemnego smaku substancji leczniczej jest możliwe dzięki rozwojowi wielu technik umożliwiających ten proces, co z kolei może znaleźć przełożenie na bardziej regularne przyjmowanie leków przez pacjenta wg odpowiednich zaleceń. Maskowanie nieprzyjemnego smaku API (ang. Active Pharmaceutical Ingredient) można osiągnąć za pomocą różnych metod. Celem artykułu jest omówienie kilku najpopularniejszych, a mianowicie wykorzystujących dodatek aromatów i/lub substancji słodzących, mikroenkapsulację, zmiany reologiczne, tworzenie kompleksów inkluzyjnych, granulację, emulsję wielokrotne, żywice jonowymienne oraz zastosowanie liposomów. Należy zaznaczyć, że wybór odpowiedniej metody powinien być ukierunkowany kilkoma aspektami, w tym przede wszystkim właściwościami fizykochemicznymi stosowanej substancji leczniczej, częstotliwością dawkowania, a także postacią leku.
... In-Vitro drug releaseIn-Vitro drug release was carried out using USP type II Dissolution apparatus (paddle) at 37±0.5 °C, 50 rpm and 900mL Simulated salivary fluid (pH 6.8) as dissolution medium. Aliquots of 5 mL were withdrawn at specified intervals of time. ...
Objective: The objective of the current research work was to prepare a taste-masked Orodispersible tablet of Nateglinide which improve patient compliance. Method: Taste Masked ion exchange resins were selected based on the preliminary studies and the process parameters of the Solvent evaporation method were also finalized by the same. 3 2 full factorial design was used for optimization. A mole of Kyron T-114 and % of Aspartame was taken as independent variables X1 & X2 respectively. % Drug release at 15 minutes, wetting time, Disintegration time, Water absorption ratio and Ability of taste masking were taken as dependent variables. Short term accelerated stability studies were performed for tablets prepared using optimized Orodispersible Tablet. Results and Discussion: Optimized batch composition had 1 Mole (49 mg) of Kyron T-114, 60 mg of Nateglinide and 3.31%(9.9 mg) Aspartame was prepared based on the values of the dependent variable of the design batches. All the evaluation parameters of the optimized batch met the acceptance criteria. The taste was improved as compared to pure Nateglinide. % In-vitro Drug release was found to be 94.40% at 15 minutes, In-vitro Disintegration Time 29 second and Taste masking as per taste panel gives the very slightly bitter for Optimized Orodispersible tablet. Stability data were also in the range of acceptance. Conclusion: A Taste masked Orodispersible tablet was developed successfully by the Solvent evaporation method.
... However, FDFs containing LCD as solid dispersions with gelatine exhibited signifcantly lower scores for taste masking ability (LF-5 and LF-6; p < 0.05) and (LF-7; p < 0.001) compared to LF-4. Te success of producing palatable FDFs of LCD was made more pronounced by the incorporation of LCD as a solid dispersion with gelatine at a weight ratio of 1 : 1 into FDFs, which indicated that G-protein coupled receptors are shielded from the efects of LCD since the latter is dispersed uniformly across the gelatine crust [38]. In addition, efective taste masking can also be attributed to the favours. ...
One of the most important issues for bitter-tasting drugs such as levocetirizine dihydrochloride (LCD) is the production of palatable dosage forms. LCD also has a delayed onset of action following oral administration. In this study, solid dispersed fast-dissolving films (FDFs) of LCD using the solvent casting method for oral application were prepared and evaluated. The FDF is composed of HPMC as the film forming polymer and different types of superdisintegrants (sodium starch glycolate, croscarmellose sodium, or crospovidone). FDF containing crospovidone showed the highest percentage release of the drug (100.54% ± 1.47 within 3 min.) and was chosen for fabricating into palatable solid dispersed FDFs using different ratios of gelatine. The results of Raman and FTIR revealed that the drug’s crystalline structure has been disrupted, and the drug has intermolecular hydrogen bonds with gelatine. The solid dispersed FDF (LF-7), which contained the drug in the form of a 1 : 1 solid dispersion with gelatine, showed a rapid in vitro disintegration (25 seconds) and a burst release of the drug (99.22% ± 2.22 within one min). The in vivo studies were conducted on human participants and showed a significant ( p < 0.05 ) reduction in disintegration time (9.43 ± 2.16 sec.) and higher taste masking ability of the solid dispersed FDF (LF-7) compared to the nonsolid dispersed FDF (LF-4). The stability studies indicated that the prepared FDF remained stable over three months. Overall, FDFs of levocetirizine dihydrochloride with a palatable and rapid onset of action were developed to relieve allergic symptoms.
... Regarding bitterness, the use of sweeteners, some amino acids, or flavor enhancers on their own does not give satisfying results, as shown by some studies. [5][6][7][8] NTF is a chemotherapeutic agent belonging to nitrofurans introduced to clinical practice in 1952. NTF is a synthetic antimicrobial agent active on both Gram-positive and Gram-negative microorganisms, obtained by the addition of a nitro group and hydantoin to a furan, a synthetic derivative of imidazolidinedione (Fig. 1). ...
Aim : To evaluate the stability of nitrofurantoin suspended in different extemporaneously compounded vehicles after storage at 4°C and at 25°C. To formulate an effective, readily available vehicle that can guarantee extended stability and precise dosing.
Materials and methods : Nitrofurantoin was suspended at a concentration of 10 mg/mL in seven different vehicles compounded of different blends of Syrupus simplex, sorbitol 70%, methylcellulose 1%, gummi arabici 1%, gummi xanthani 1%, and sodium carboxymethylcellulose (NaCMC) 1%. Samples of 100 mL of every compounded suspension were stored in dark in graded glass bottles at 4°C and at 25°C. Samples were analyzed at the beginning and every 10 days up to day 30 and every 30 days after. Variations of physical properties such as sedimentation, ease of resuspension, color and odor were evaluated visually and organoleptically. Rheological analysis was also performed in order to determine suspensions’ behavior during storage and dosing. Variations in nitrofurantoin concentration and pH were evaluated with suitable analytical procedure (UV-Vis; HPLC; pH/ORP). Microbiological stability was evaluated via incubation on suitable culture media.
Results : To the 30th day, only three of the compounded suspensions exhibited significant physical stability and slight change in taste and odor stored at both temperatures. Two samples stored at 25°C exhibited nitrofurantoin concentration greater than 95% and 4 samples stored at 4°C – concentration greater than 95%. All models showed no microbial growth up to day 30. At 120 days, only three of the compounded suspensions, stored at 4°C, exhibited relatively high nitrofurantoin concentrations: 88.2%, 92%, and 81.1%, respectively. Only one model suspension showed chemical and physical stability (≥95% of the initial concentration) for 102 days. No model suspension remained sterile after 30 days.
Conclusions : The suspensions compounded with vehicles of blends of syrups, xanthan, croscarmellose (NaCMC), and sorbitol exhibited low to none sedimentation, good uniformity of content and are suitable organoleptically for pediatric administration. The model suspension stored at 4°C (NTF VII 4°C – with major excipients: sucrose 16%, sorbitol 17%, xanthan gum 0.25%, NaCMC 0.25%) stands out with nitrofurantoin concentration higher than 95% along with no or little signs of sedimentation. After adding a suitable preservative agent or system, a formulation with these characteristics might have an expiration date of at least 90 days.
... To improve patient adherence to medication, proven methods for reduction and inhibition of bitter taste have resulted in improved palatability of these formulations (Kleinert et al., 1993). Taste is a function of sensation by the taste buds in the mouth and for formulations intended for geriatric, non-cooperative and bed ridden patients, the main challenge is to mask the taste of bitter drugs, to enhance patient acceptability and to ensure they will receive the optimal therapeutic dose of their medication (Momin et al., 2012). Some of the methods employed in taste masking include coating of bitter drug particles with coating agents such as starch, polyvinyl pyrrolidone, gelatin and ethyl cellulose (Gowthamarajan et al., 2004). ...
This study reports the development and characterization of taste masked, freeze-dried composite wafers for potential oral and buccal delivery of low dose aspirin (acetylsalicylic acid) to prevent thrombosis in elderly patients with dysphagia. The wafers were formulated by combining metolose (MET) with carrageenan (CAR), MET with chitosan (CS) at low molecular weight or CAR with CS using 45% v/v ethanol as solvent for complete solubilization of acetylsalicylic acid. Each wafer contained 75 mg of acetylsalicylic acid and sweetener (sucralose, stevia or aspartame) with a drug: sweetener ratio of 1:1 w/w. The formulations were characterized for physical properties using texture analyzer (hardness and mucoadhesion), scanning electron microscopy (SEM), X-ray diffractometry (XRD), Fourier transform infrared (FTIR) spectroscopy, swelling capacity, and in vitro drug dissolution. Further, permeation studies with three different models (Permeapad™ artificial barrier, EpiOral™ and porcine buccal mucosa) using HPLC, cell viability using MTT assay and in vivo taste masking evaluation using human volunteers were undertaken. The sweeteners increased the hardness and adhesion of the wafers, XRD showed the crystalline nature of the samples which was attributed to acetylsalicylic acid, SEM confirmed a compacted polymer matrix due to recrystallized acetylsalicylic acid and sweeteners dispersed over the surface. Drug dissolution studies showed that acetylsalicylic acid was rapidly released in the first 20 min and then continuously over 1 h. EpiOral™ had a higher cumulative permeation than porcine buccal tissue and Permeapad™ artificial barrier, while MTT assay using Vero cells (ATCC® CCL-81) showed that the acetylsalicylic acid loaded formulations were non-toxic. In vivo taste masking study showed the ability of sucralose and aspartame to mask the bitter taste of acetylsalicylic acid and confirm that acetylsalicylic acid loaded MET:CAR, CAR:CS and MET:CS composite wafers containing sucralose or aspartame have potential for buccal delivery of acetylsalicylic acid in geriatric patients with dysphagia.
... Additionally, several production techniques can be used to manufacture different oral preparations. [3] However, conventional dosage forms such as tablets and capsules are not suitable for the paediatric population due to swallowing difficulty and a high risk of choking. [4,5] Therefore, liquid preparations are relatively more acceptable for children. ...
Objectives:
A child-friendly taste-masking strategy using solid lipid microsphere (SLM) has been proposed to obscure the undesirable taste of some water-soluble drugs. In this study, the reversed lipid-based nanoparticle (RLBN) technique was used to encapsulate a water-soluble drug to facilitate the preparation of SLM.
Methods:
The model drug used was atomoxetine hydrochloride (ATX), and a three-step method was used to prepare ATX-RLBN. Taste-masking microsphere (ATX-RLBN-SLM) was prepared by the spray chilling method. The drug release mechanism was studied by high-performance liquid chromatography and scanning electron microscopy. Moreover, in vitro taste evaluation method was established and ATX bioavailability was investigated employing pharmacokinetic studies.
Key findings:
The obtained ATX-RLBN-SLM had smooth spherical particles with a size of about 80 μm. The drug encapsulation and loading efficiencies were 98.28% ± 0.59% and 0.89% ± 0.04%, respectively. In vitro drug release studies showed that nearly 96% drug was retained in the microspheres within 10 min at pH 6.8 and a complete release was triggered by lipase, accompanied by variation in the morphology. Taste assessment revealed that ATX-RLBN-SLM could efficiently mask the bitter taste and improved the bioavailability of ATX.
Conclusions:
Atomoxetine hydrochloride-reversed lipid-based nanoparticle-solid lipid microsphere exhibited excellent taste-masking effect with negligible leakage in the oral cavity environment and thorough collapse upon lipase stimulation, simultaneously enhancing the bioavailability of ATX. The study paves a new way to efficiently mask the undesirable taste of some water-soluble drugs.
... effective, and easily available natural superdisintegrant from banana fruit to offer secure and effective drug delivery meloxicam as MDTs with better patient fulfillment or acceptance [14]. ...
Objective: The objective of the present work was the preparation and evaluation of mouth dissolving tablets (MDTs) of meloxicam using natural superdisintegrants. Methods: Meloxicam is BCS Class II (low soluble, and high permeable) drug increasing the dissolution properties of the poorly water-soluble drug meloxicam using a solid dispersion method (solvent evaporation method). Solvent evaporation method using drug and carrier as polyethylene glycol (PEG)-6000 and PEG-15,000 the ratio of 1:1, 1:2 (drug:carrier), and acetone as solvent. In house prepared banana powder were used as natural superdisintegrant. Manufacturing of MDT was done by the direct compression method. In this MDTs, various excipients were used such as mannitol used as the diluent, sodium saccharin used as a sweetening agent, Avicel pH-102 used as a binding agent, and talc and sodium lauryl sulfate (SLS) used as lubricant and glidant. The best formula of the tablet was selected according to the disintegration time (DT) and friability tests. Results: The results have shown that an increase in the meloxicam solubility was obtained using solid dispersion with the solvent evaporation method using PEG-15000 as a carrier in the ratio of 1:2 (drug:carrier). Taste masking was also done by a solid dispersion method. Tablet prepared with in house prepared banana powder gave less DT (70 s) as compared to tablet prepared with branded banana powder (80 s), but formulation F5 failed in friability testing. Improved strength of tablet obtained using SLS (<1%) also showed an increase in the dissolution performance of the tablet in formulation F6. This F6 formulation having 10% natural super disintegrating agent (in house prepared banana powder) has shown 99% cumulative drug release within 18 min. It also passed the friability test. Conclusion: Accordingly, the solubility of meloxicam was successfully enhanced through solid dispersion with carrier PEG-15,000 and formulated as a MDT to improve its oral absorption. PEG has also been used as a taste masking agent in these formulations. It was concluded that in house banana powder had excellent DT as compared to branded banana powder. Banana powder is “economical” and “easily available” than other commonly used synthetic superdisintegrants. The process of banana powder preparation is eco friendly. The meloxicam MDT formulated with natural superdisintegrant in house prepared banana powder found to pass all pharmacopeial tests.
... weight) of these multiparticulates depending on the patient's body weight. 4 Quinine Sulphate is slightly soluble in water. An additional formidable challenge for an oral Quinine Sulphate formulation is its extremely bitter taste. ...
Introduction: Quinine Sulphate is an antimalarial agent usually indicated in the treatment of chloroquine resistant malaria. Objective: The objective of the present investigation was to prepare quinine sulphate loaded solid lipid nanoparticles by ultrasonic solvent emulsification technique using different surfactants (Tween 80, Poloxamer 407, Poloxamer 188) in order to mask the bitter taste, thereby improving patient compliance and to provide dose precision and a flexible system that allows dose adaptation according to the body weight. Method: Glyceryl monostearate was used as a lipid (drug to lipid ratio 1:3). The prepared solid lipid nanoparticles were characterized for various parameters like particle size and shape, zeta potential, entrapment efficiency, In vitro evaluation of taste masking efficiency, In vitro drug release, In vitro drug release kinetics. Results and discussion: The mean hydrodynamic diameter of the particle decreased whereas the entrapment efficiency increased with an increase in the surfactant concentration. Higher surfactant concentration showed faster In vitro release. The formulations showed negligible release at pH 6.8 and almost 100% release at pH 1.2, which is desirable so as to mask the taste by delaying the release during administration without hampering the drug release in stomach. Formulation F9 containing 2% w/v poloxamer 188 was selected as the optimized formulation as it showed high entrapment efficiency and negligible release in Simulated Salivary Fluid (SSF) pH 6.8 when compared to pure drug but showed almost 100% release at pH 1.2. Conclusion: It can be concluded that quinine sulphate was proven to be a suitable candidate for formulating solid lipid nanoparticles to achieve better patient compliance among pediatric and geriatric populations by masking the bitter taste and avoiding the difficulty in swallowing. © 2014, Association of Pharmaceutical Teachers of India. All rights reserved.
... Other approaches are coaservation phase separation [10], ion exchange resins [11], solid dispersions [12] and extrusion methodP P [13] have all been used to mask the disagreeable taste of the API. The aim of this study is to develop a successful method to cover the bitter taste of previously prepared Prifinium Bromide (PBr) ODT [14] by trying different techniques and the preparation of a taste masked ODT using a previously prepared formula. ...
Objective: In previous work, Prifinium Bromide had been successfully formulated as oro-dispersible tablets. However, Prifinium Bromide, a quaternary ammonium compound, has a bitter taste; therefore, taste masking was necessary to produce acceptable oro-dispersible tablets and enhance patients' compliance.
... For drug therapy adherence and patient convenience, tastemasking of unpleasant tasting active pharmaceutical ingredients (APIs) is desirable. Many research and developing groups spend tremendous effort on developing taste-masked formulations, whereof several approaches have been derived (Momin, 2012). One taste-masking approach is to construct physical barriers as realized in coated tablets or granules. ...
The aim of this work was to produce and characterize taste-masked powders of a model drug (acetaminophen) prepared using potentially tolerable and safe excipients for paediatric use, i.e. sodium caseinate and lecithin. The powders were produced by spray-drying aqueous dispersions. The characteristics of taste-masked drug particles were determined by scanning electron microscopy, differential scanning calorimetry and X-ray photoelectron spectroscopy to analyse the surface composition of particles. Taste assessment was approached by an indirect method through drug release studies. We developed a method with a syringe pump using small volumes of aqueous medium and low flow rates, to mimic the behaviour in the mouth. This method was compared to the electronic tongue analysis. SEM, DSC and XPS analysis indicated differences in surface composition of spray-dried particles according to the caseinate/lecithin ratio and to relate it with taste-masking. The "coating" consisting of caseinate and lecithin had a significant role in decreasing the release of drug during the first 2 min and so in taste-masking. Higher content in lecithin results in higher taste-masking efficiency. The association of sodium caseinate and lecithin seems to be promising to mask the bitterness of acetaminophen. A good agreement between release study and electronic tongue analysis was established.
Taste has an important role in the development of oral pharmaceutical formulation, with respect to patient compliance. Hence, pharmaceutical companies invest time, money and resources in developing palatable and pleasant tasting products and adopt various taste masking techniques to develop an appropriate formulation. Taste assessment is one of the important quality-control parameter for evaluating taste-masked formulations. To date, several innovative in vivo approaches, in vitro drug release studies utilizing taste sensors, specially designed apparatus and drug release by modified pharmacopoeial methods have been reported in the literature for assessing the taste of drugs or drug products. The most widely used method is psychophysical evaluation by a human taste panel. It may be suitable for product development, but not typically acceptable for product quality control. In vitro methods, direct or indirect, must be developed at some point to support commercial production. More recently, Biomimetic taste sensing systems (BMTSSs) with combined use of multivariate data analysis (MVDA) has been demonstrated to be a powerful tool in taste measurement technology. BMTSSs have been marketed as taste sensors, or electronic tongues or e-tongues. An e-tongue, was first proposed and patented by Toko's group in 1989, and subsequently abundant research has been performed on the application of e-tongues to the valuation of taste and quality of foods or medicines. The taste-sensing systems SA401 and SA402B, the Alpha MOS electronic tongue Astree2 and the Insent taste sensing system TS-5000Z have been developed for high-throughput taste screening and quality control. These instruments employ electrochemical sensors coupled with chemometric methodologies to perform qualitative and quantitative analyses of organoleptic and chemical properties of substances and products. The instrument, however, is very heavy and expensive. Some research groups have proposed portable-type, miniaturized or disposable taste sensor systems. However, practical implementations of these types of taste sensor, which might address the limitations of conventional laboratory analyses, have not yet been reported. BMTSSs have been shown to be globally selective for detecting and quantifying specific classes of chemical compounds. As we discuss here, the latest trends in the taste assessment of pharmaceuticals will result in a decreased reliance on human panel tests. Please cite this article in press as Malode Sarika S. et al. Taste masking: overview of taste assessment approaches in the development of oral pharmaceutical formulations.
Polyethylene glycol (PEG) are widely applied in detergents, cosmetics, and food additives. A simultaneous analytical method was developed to detection the polyethylene glycol (100–10000 Da). High-performance liquid chromatography (HPLC) with evaporative light scattering detector (ELSD) could analyze successively PEG products. The method was verified with liquid chromatography–electrospray ionization mass spectrometry (LC-ESI-MS/MS). The retention times of PEG 200–8000 ranged from 1.97 to 12.33 min. Method validation was performed to the International Conference on Harmonization (ICH) guidelines and the Korea Ministry of Food and Drug Safety (MFDS); linearity: R²>0.997, LOD: 7.47–16.24 µg/mL, LOQ: 22.40–75 µg/mL, repeatability (%RSD): 0.2–2.5, recovery (%): 90.4–104.9% for film-coated tablet, 80.1–95.9% for sugar-coated tablet. A total of 115 PEG could be identified by extracted ion chromatography in mass analysis, based on the charge state represented as [M+Na⁺+H3O⁺n-1]. This method can be applied for successive identification of PEGs in PEG-containing products.
Chewable tablets are easy-to-use dosage formulations and widely applied in pediatric dosage forms. However, the chewable tablets have to disintegrate in the mouth before swallowing, which makes the chewable tablet dosage forms inappropriate for bitter active ingredients. In this study, a polymer (Eudragit® EPO) and/or wax (cetyl alcohol, stearic acid, or beeswax) dispersion technique has been used to overshadow the unpleasant taste of paracetamol. The chewable tablet made from Eudragit® EPO dispersion showed low disintegration and dissolution due to its low water solubility. While the wax or the mixture of cetyl alcohol and Eudragit® EPO-based tablets had fast disintegration (11.50–35.40 s) and the drug release were >90% in 45 min. The taste-masking study in human volunteers revealed that the chewable paracetamol tablets prepared from drug dispersion improved the taste of the paracetamol chewable tablets without wax/Eudragit® EPO dispersion. The mixture of cetyl alcohol and Eudragit® EPO dispersion could mask bitter taste better than those of cetyl alcohol. In conclusion, cetyl alcohol together with Eudragit® EPO could be efficiently used in the formulation of taste-masked paracetamol chewable tablets that complied with the United States Pharmacopeia standard.
Taste masking is of critical importance for active ingredients with an undesirable taste, due to the need for increased patient compliance, especially in pediatric and geriatric population. Various techniques for taste masking involve addition of flavours, sweeteners and amino acids, use of effervescent agents, prodrug formation, salt preparation, adsorption, formation of complex with ion- exchange resins, inclusion complexes and molecular complexes, microencapsulation, granulation, viscosity modifiers, multiple emulsion, liposomes and solid dispersion systems. In pharmaceutical industry, taste masking involves the development of a system that prevents the active substance from interacting with taste buds, thereby reducing the negative sensory response. This article reviews the different technologies which are used for masking the bitter taste and methods for evaluation of taste masking efficacy.
The palatability of a pediatric drug formulation is one of the key prerequisites for therapeutic success. Liquid formulations are often chosen for pediatric drug products, and they require special attention regarding their taste, as they have direct contact to the taste buds and a relatively long residence time in the oral cavity. For ethical reasons, the role of electronic tongues in the development of oral drug formulations with new chemical entities (NCEs) for pediatric use is growing, however, little is known about the strategies how this instrumental taste assessment can be performed.
The present study illustrates two possibilities to combine in-vitro and in-vivo data for the characterization of the palatability of the new drug candidates CSE3104 and CSE3165. As a first step, the implementation and suitability of electronic tongue measurements has been demonstrated by comparison of in-vivo and in-vitro data. In alignment with the taste assessment results during a single-center, double-blinded, randomized, placebo-controlled, single ascending dose (SAD) study in healthy subjects, the bitter taste perception of CSE3104 was assessed with e-tongue measurements. Moreover, the sensor response pattern showed comparable results of the e-tongue measurements to the human taste study of CSE3165: With increasing concentration, the bitterness values were increased. In addition, the human taste pattern showed increasing values for sourness due to higher volumes of the citric acid buffer. Results of the hedonic descriptor “unpleasant” within the human taste assessments could be related to bitterness in the instrumental taste assessment.
For the second step in electronic tongue guided formulation development two possibilities are depicted in the article focusing on the effect of different excipients on the formulation on the one hand and on the assessment and comparison of two drug formulations on the other hand.
Based on these results, the low number of healthy volunteers for the taste assessment in a Phase 1 study led to a meaningful interpretation, by applying in addition the electronic tongue. Using this instrumental approach led to reproducible data versus the human taste assessment, without ethical concerns, and with a reduction in time and costs.
In this work a potentiometric electronic tongue based on classical ion-selective electrodes (6 types) and solid contact electrodes (2 types) was applied. The classical electrodes based on PVC membrane with other plasticizers exhibited cation-, anion-, amine-, and carbonate sensitivity, while the solid contact electrodes based on different lipophilic salts established diclofenac sensitivity. These sensors were used to assess the taste masking efficiency of diclofenac using selected sweeteners and cyclodextrin. Various amounts of four sweeteners (namely: sucrose, lactose, acesulfame K, sodium saccharin) as well as 2-hydroxypropyl-β-cyclodextrin were applied to mask the bitter taste of diclofenac. The signals of the sensor array registered during the experiments were processed by the Principal Component Analysis. The results obtained i.e. the chemical images of the samples indicated that the taste masking effect was the most pronounced for cyclodextrin, acesulfame K, sodium saccharin and for sucrose at higher concentration, whereas was almost negligible in the case of the presence of lactose in solution.
Manipulation of liquid oral drugs by mixing them into foodstuff is a common procedure for taste-masking of OTC pharmaceuticals when administered to children. However, the taste-masking capability of such application media is not systematically evaluated, and recommendations for suitable media are hardly published. In this study, a sensor array of commercially available and self-developed electronic tongue sensors was employed to assess the taste-masking efficiency of eight different beverages (tap water, apple juice, carrot juice, fennel tea, fruit tea, milk, cocoa, and Alete meal to drink) on the OTC pharmaceuticals Ambroxol-ratiopharm®, Cetirizin AL, and Laxoberal® by multivariate data analysis. The Euclidean distances between each pure application medium and its corresponding drug mixture were used as an indicator for the taste-masking efficiency and correlated to the physico-chemical properties of the beverages. Thus, the pH value, the viscosity, as well as the fat and sugar content of the beverages were included, whereas only the viscosity appeared to be insignificant in all cases. The sugar content as well as the fat content and pH value emerged to be a significant variable in taste-masking efficiency for some of the tested drug products. It was shown that the applied electronic tongue sensors were capable to demonstrate the impact of the physico-chemical properties of the application media on their taste-masking capacity regardless of their non-selectivity towards these characteristics.
Approaches to improve the taste of oral dosage forms that contain unpleasant tasting drugs are versatile. Likewise, the analytical in vitro and in vivo methods to assess taste-masking efficacy are diverse. Taste-masking has gained in importance since the EU legislation on medicines for children came into force in 2007, and taste-masking attributes are often required by regulatory authorities. However, standardized guidance for the analytical evaluation is still poor. Published protocols rarely consider real conditions, such as the volume of saliva or the residence time of solid oral dosage forms in the mouth. Methodological limitations and problems regarding time point of evaluation, sampling or sample pretreatment are hardly ever addressed. This critical review aims to evaluate and discuss published strategies in this context.
Taste is most important organoleptic aspects about the acceptance of oral drugs. Bitter and unpalatable taste is a major problem of certain drugs in formulations. In market, there are numbers of pharmaceutical preparations available in which actives are bitter in taste. The improved palatability in these products has prompted the development of numerous formulations, which improved performance and acceptability. The bitterness of preparation also leads to patient incompliance. So masking of bitterness becomes essential and done by masking the bitter taste of drugs by either decreasing its oral solubility on ingestion or decreasing the amount of drug particles exposed to taste buds thereby reducing the perception of bitter taste. Methods commonly used for taste masking involves various physical and chemical method that prevent the interaction of taste bud with drugs and are based on coatings, solid dispersion system and ion exchange resin, entrapment method and masking of taste buds etc. Taste masking of bitter drugs become necessity in case of oral administration and selection of technology depends upon the bitterness of drugs and their compatibility with taste masking agents that does not affect the bioavailability of drug
Taste is an important factor in the development of dosage form. Nevertheless it is that arena of product developmentthat has been overlooked and undermined for its importance. Taste masking technologies offer a great scope forinvention and patents. Several approaches like adding flavors and sweeteners, use of lipoproteins for inhibitingbitterness, numbing of taste buds, coating of drug with inert agents, microencapsulation, multiple emulsion, viscositymodifiers, vesicles and liposomes, prodrug formation, salt formation, formation of inclusion and molecular complexes,solid dispersion system and application of ion exchange resins have been tried by the formulators to mask theunpleasant taste of the bitter drugs. The present review attempts to give a brief account of different technologies oftaste masking with respect to dosage form and novel methods of evaluation of taste masking effect.
According to the year 2003 survey of pediatricians by the American Association of Pediatrics, unpleasant taste was the biggest barrier for completing treatment in pediatrics. The field of taste masking of active pharmaceutical ingredients (API) has been continuously evolving with varied technologies and new excipients. The article reviews the trends in taste masking technologies by studying the current state of the art patent database for the span of year 1997 to 2007. The worldwide database of European patent office (http://ep.espacenet.com) was employed to collect the patents and patent applications. It also discusses the possible reasons for the change of preferences in the taste masking technologies with time. The prime factors critical to the selection of an optimal taste masking technique such as the extent of drug bitterness, solubility, particle characteristics, dosage form and dose are briefly discussed.
Beclamide was microencapsulated in order to mask the taste, by a simple coacervation method using gelatin. Anhydrated sodium sulphate was used as coacervating agent. Glutaraldehyde, glutaraldehyde:isopropanol (8 : 32) and formaldehyde:isopropanol (8 : 32) were used as hardening agents. The optimum microencapsulation conditions were: 44 g water, 9 g beclamide and 47 g sodium sulphate as components at a temperature of 40 + 0.5 degrees C with glutaraldehyde (25 per cent w/v) as hardening agent. The dissolution rate of beclamide from prepared microcapsules was determined by a rotating basket and the dissolution kinetics were investigated according to the zero-order, Hixson-Crowell and Higuchi equations. The dissolution pattern of beclamide was first-order kinetic. Release rate constants, t50%, t90% and AUC values were calculated. All these values were discussed for differently obtained microcapsules. Beclamide was formulated in conventional, chewable and effervescent tablet forms. Physical tests were applied to all tablets. The paddle method was used as an in vitro dissolution test method for evaluation of conventional tablets.
Recent research on cellular mechanisms of peripheral taste has defined transduction pathways involving membrane receptors, G proteins, second messengers, and ion channels. Receptors for organic tastants received much attention, because they provide the specificity of a response. Their future cloning will constitute a major advance. Taste transduction typically utilizes two or more pathways in parallel. For instance, sweet-sensitive taste cells of the rat appear to respond to sucrose with activation of adenylyl cyclase, followed by adenosine 3',5'-cyclic monophosphate (cAMP)-dependent membrane events and Ca2+ uptake. The same cells respond differently to some artificial sweeteners, i.e., with activation of phospholipase C (PLC) followed by inositol 1,4,5-trisphosphate (IP3)-dependent Ca2+ release from intracellular stores. Some bitter tastants block K+ channels or initiate the cascade receptor G1 protein, PLC, IP3, and Ca2+ release or the cascade receptor alpha-gustducin, phosphodiesterase (PDE), cAMP decrease, and opening of cAMP-blocked channels. Membrane-permeant bitter tastants may elicit a cellular response by interacting with G protein, PLC, or PDE of the above cascades. Salt taste is initiated by current flowing into the taste cell through cation channels located in the apical membrane, even though basolateral channels may also contribute (following salt diffusion through paracellular pathways). In rodents, the Na+-specific component of salt taste is typically mediated by apical amiloride-sensitive Na+ channels, but less specific and not amiloride-sensitive taste components exist in addition. Sour taste may in part be mediated by amiloride-sensitive Na+ channels conducting protons, but other mechanisms certainly contribute. Thus the transduction of taste cells generally comprises parallel pathways. Furthermore, the transduction pathways vary with the location of taste buds on the tongue and, of course, across species of animals. To identify these pathways, to understand how they are controlled and why they evolved to this complexity are major goals of present research.
This study addresses how to mask the undesirable taste of diclofenac sodium (DS) without interfering with an adequate rate of drug release. DS microcapsules were successfully prepared using a system of ethylcellulose (EC)-toluene-petroleum ether. The system was optimized by the construction of the phase diagram and determination of the amount of EC precipitated under different solvent:non-solvent ratios to determine the most appropriate conditions for preparing good microcapsules. Microcrystalline cellulose (Avicel) and lactose were mixed with DS powder and converted into spherical cores by the wet agglomeration technique which facilitated coacervation and formation of thin and uniform microcapsule walls. Diethylphthalate (DEP) and Polyethyleneglycol 600 (PEG) in different concentrations (20 or 40% w/w) were used as plasticizers to impart better elasticity to the microcapsules. The microcapsules were evaluated for DS released against crushed commercial DS enteric coated tablet (Voltaren). The prepared microcapsules were taste evaluated by a taste panel of 10 volunteers. The results revealed that the optimum solvent:non-solvent ratio required for microcapsule formation was 1:2. Microcapsules containing PEG 20% or DEP 40% showed a faster rate of DS release compared to that obtained from other microcapsules and crushed commercial enteric coated tablets (Voltaren). The palatability and the taste of DS were significantly improved by microencapsulation. The extent of taste masking was influenced by the microcapsule core:wall ratio, the presence of additives within the core, the type and concentration of plasticizer and initial core size.
Taste is one of the most important parameters governing patient compliance. Undesirable taste is one of several important formulation problems that are encountered with certain drugs. Oral administration of bitter drugs with an acceptable degree of palatability is a key issue for health care providers, especially for pediatric patients. Several oral pharmaceuticals, numerous food and beverage products, and bulking agents have unpleasant, bitter-tasting components. So, any pharmaceutical formulation with a pleasing taste would definitely be preferred over a competitor's product and would translate into better compliance and therapeutic value for the patient and more business and profits for the company. The desire of improved palatability in these products has prompted the development of numerous formulations with improved performance and acceptability. This article reviews the earlier applications and methodologies of taste masking and discusses the most recent developments and approaches of bitterness reduction and inhibition for oral pharmaceuticals.
The purpose of this research was to formulate tasteless complexes of ciprofloxacin with Indion 234 and to evaluate molecular properties of drug complexes. The effect of batch and column process, complexation time, temperature, and pH on ciprofloxacin loading on Indion 234 is reported. Drug resin complexes (DRC) were characterized by infrared spectroscopy, thermal analysis, and x-ray diffraction pattern. Ciprofloxacin release from DRC is obtained at salivary and gastric pH and in the presence of electrolytes. The efficient drug loading was evident in batch process using activated Indion 234 with a drug-resin ratio of 1:1.3. Drug complexation enhanced with pH from 1.2 to 6, while temperature did not affect the complexation process. Infrared spectroscopy revealed complexation of -NH (drug) with Indion 234. DRC are amorphous in nature. Drug release from DRC in salivary pH was insufficient to impart bitter taste. Volunteers rated the complex as tasteless and agreeable. Complete drug release was observed at gastric pH in 2 hours. The drug release was accelerated in the presence of electrolytes. Indion 234 is inexpensive, and the simple technique is effective for bitterness masking of ciprofloxacin.
The basic objectives of this study were to prepare and characterize solid dispersions of poorly water-soluble drug etoricoxib using lipid carriers by spray drying technique. The properties of solid dispersions were studied by diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS), differential scanning calorimetry (DSC), hot-stage microscopy (HSM), radiograph powder diffraction (XRPD), and dissolution studies. The absence of etoricoxib peaks in XRPD profiles of solid dispersions suggests the transformation of crystalline etoricoxib into an amorphous form. In the HSM examination of solid dispersions, the dissolution of drug in the lipid carriers was observed, which was also confirmed by the absence of etoricoxib peak in DSC curves of solid dispersions. The DRIFTS spectra revealed the presence of hydrogen bonding in solid dispersions. The in vitro dissolution test showed a significant increase in the dissolution rate of solid dispersions as compared with pure etoricoxib, spray-dried etoricoxib, and physical mixtures of drug with lipid carriers. Therefore, the dissolution rate of poorly water-soluble drug etoricoxib can be significantly enhanced by the preparation of solid dispersions using lipid carriers by spray drying technique.
Oral administration of pharmaceuticals is one of the most popular method of drug dilevery. Many orally administered drugs elicit bitter taste. Palatability is an extremly important factor in ensuring the likelihood that the recepient will intake the pharmaceuticals. A constant problem is in treatment of patient is their inability or unwillingness to swallow solid dosage form such as tablets specially in children and the elderly. These dosage form permit perceptible exposure of active drug ingredient to the taste bud. Accordingly, masking of unpleasent taste characterstics of drug is an important factor in formulation of these agents."The worse the taste of the medication, the better the cure" was once the prevailing attitude. Today a change in patient attitude and development of taste masking technique has reversed this opinion. Patients now expect and demand formulations that are pleasently, or atleast tolerably, flavored.1 This article reviews the earlier methodologies and approaches of taste masking of bitterness reduction.
The influence of heat treatments on the dissolution and the masking degree of the bitter taste for the coated fine granules with water-insoluble film composed of ethylcellulose, hydroxypropylmethylcellulose, titanium dioxide and sucrose fatty acid ester (SS) (4:2:1:1), containing sparfloxacin (SPFX) and low-substituted hydroxypropylcellulose in the cores was investigated. The dissolution rate of SPFX from the coated fine granules in water was increased by heat treatment of the granules. Dissolution percentage at 30 min in water after heat treatment at 70°C for more than 4h reached almost 100%, whereas it was about 90% before the heat treatment. The masking degree of the bitter taste for the coated fine granules was improved by the heat treatment. Differential scanning calorimetry (DSC) analysis of the coating film indicates that the endothermic peak due to melting of SS in the film disappeared with the heat treatment at 70°C for 4 h, and also that the tensile strength of the film was reduced to one-half of the initial value after the heat treatment. It is thought that heat treatment caused changes of film properties, i.e. that tensile strength and wettability are attributable to the melting and diffusing of SS in the film, resulting in the dissolution level being increased to about 100% and the masking degree of the bitter taste being greatly improved.
Acceptability of any drug dosage form mainly depends over its taste i.e. mouth feel. drug molecule interacts with taste receptor on the tongue to give bitter, sweet or other taste sensation, when they dissolve in saliva. This sensation of taste is the result of signal transduction from the receptor organs for taste, commonly known as taste buds. Now a days most of the potent drugs that may be cardiac, analgesics, anti inflammatory, anti tubercular, anthalmentics, antibacterial, anticoagulants, anti epileptics, antimalarials, anti neoplastics, anti thyroids, antiprotozoal, diuretics, histamine receptor antagonists, nutritional agents, opioids analgesics, oral vaccines and sex hormones, most of them are bitter in taste. So it becomes necessary to develop such a dosage for that must be acceptable in taste to patient especially in case of children or geriatrics. To overcome this problem so many techniques are available to mask the bitter taste of drugs. These techniques are not only serves as to mask the taste of drug as well as to enhance the bioavailability of drug dosage form. Commonly used techniques that are adopted for large scale production of pharmaceutical dosage form are use of flavors, coating of drug particle with inert materials, by formation of inclusion complexes, by Molecular complexes of drug with other chemicals, Microencapsulation, Multiple Emulsions, Prodrugs,using liposomes, Dispersion coating and Ion Exchange Resin approach.
Taste is an important parameter in administering drugs orally and is a critical factor to be considered while formulating orodispersible, melt in mouth, buccal tablet and other formulations which comes in contact with taste buds. Undesirable and particularly bitter taste is one of the important formulation problems that are encountered with many drugs. Administration of bitter drugs orally with acceptable level of palatability is a key issue for health care providers. Proven methods for bitterness reduction and inhibition have resulted in improved palatability of oral pharmaceuticals. The problem of bitter and obnoxious taste of drug in pediatric and geriatric formulations is a challenge to the pharmacist in the present scenario. Four fundamental sensations of taste have been described: Sweet and salty, mainly at the tip. Sour, at the sides. Bitter, at the back. The present review depicts the taste-masking techniques like taste masking with flavors, sweeteners, and amino acids, lipophilic vehicles e.g. lipids, lecithin and lecithin-like substances etc and inter coating of drug particles, microencapsulation, inclusion complexes and molecular complexes of drugs with other chemicals, solid dispersions, use of multiple emulsions, liposome's, prodrugs, taste abatement by ion exchange resins and their applications in pharmaceutical formulation technology, Classification of ion exchange resins, Factors that affect IER process involved in the delivery of cationic drugs.
Solid lipid extrusion is a suitable technique to produce oral dosage forms with improved taste properties. The design of a lipid formulation for poorly water soluble drugs is a challenge because of the poor dissolution and potential bioavailability problems. In this study, solid lipid extrusion at room temperature was applied for the formulation development of the BCS Class II drug NXP 1210. Powdered hard fat (Witocan(®) 42/44 mikrofein), glycerol distearate (Precirol(®) ato 5) and glycerol trimyristate (Dynasan(®) 114) were investigated as lipid binders. Different amounts of polyvinylalcohol (PVA)-polyethyleneglycol (PEG)-graft copolymer (Kollicoat(®) IR) and crospovidone (Polyplasdone(®) Xl-10) were scrutinized as solubilizers. The dissolution profiles depicted a short lag time (about 2min) and then fast and complete dissolution of NXP 1210 by increasing the amount of crospovidone. The initial release was more delayed with an increased amount of PVA-PEG-graft copolymer. Dissolution rate could also be influenced by changing the lipid binder from pure hard fat into a mixture of hard fat, glycerol distearate and glycerol trimyristate. The formulations are feasible for taste-masked granules or pellets containing poorly soluble drugs.
In the present study, thin-coating as a potential method for improving flow properties of cohesive ibuprofen powder was introduced. Briefly, the technique was based on the successive deposition of ultrasound-assisted fine polymer mist onto the surface of the powdered active pharmaceutical ingredient (API), producing individual particles with a hydrophilic thin-coat. A 0.15% m/V aqueous solution of hydroxypropyl methylcellulose (HPMC) was used. Particle size and surface analysis revealed a decrease in the cohesiveness of ibuprofen powder and an increase in the homogeneity of particle surfaces as a result of polymer treatment. Superficial changes caused a substantial improvement on the flowing characteristics of coated substance over uncoated. The enhancement in flow rate proceeded as the uniformity of the HPMC layer increased. In conclusion, the proposed technique is a simple and effective method that can be used as a continuous process to modify API particle surface properties, which in turn improve the handling of poorly flowable powder.
Undesirable taste is one of several important formulation problems that are encountered with certain drugs. The problem of bitter and obnoxious taste of is a challenge to the pharmacist in the present scenario. Taste is an important parameter governing compliance. Several oral pharmaceuticals and bulking agents have unpleasant, bitter-tasting components. In numerous cases, the bitter taste modality is an undesirable trait of the product or formulations and can considerably affect its acceptability by consumers. Bitter characteristics found in such systems have been eliminated or minimized by various known processes, but no universally applicable technology for bitterness inhibition has ever been recognized. The desire of improved palatability in these products has prompted the development of numerous formulations with improved performance and acceptability. This paper reviews different methods are available to mask undesirable taste of the drugs, with the applications. Popular approaches in the development of taste masking are based on coating, solid dispersion system and ion exchange resin.
In recent years due to application of combinational chemistry and high-throughput screening during drug discovery, a majority of new drug candidates exhibits poor aqueous solubility, compounds to be very challenging for formulation scientists in development of bioavailable dosage forms for such.A poorly water soluble compound has classically been defined as one dissolving in less than 1part per 10000 part of water 1 A poorly water soluble drug, more recently, has been defined in general terms to require more time to dissolve in the gastrointestinal fluid than it take to be absorbed in the gastrointestinal tract2. Thus a greater understanding of dissolution and absorption behaviors of drugs with low aqueous solubility is required to successfully formulate them into bioavailable drug products.Although salt formation, partical size reduction, etc. have commonly been used to increase dissolution rate of the drug, there are practical limitation with these techniques the desired bioavailability enhancement may not always be achieved. Therefore formulation approaches are being explored to enhance bioavailability of poorly water-soluble drugs. One such formulation approach that has been shown to significantly enhance absorption of such drugs is to formulate/prepare solid dispersion.Chiou and Riegelman defined the term solid dispersion as
The interaction of polacrilin potassium, the salt of a polycarboxylic acid ion-exchange resin, with 11 amine drugs was studied. All drugs showed maximum interaction at pH 4.5-5.5. Tertiary amines exhibited a much greater affinity for the resin than primary, secondary, and quaternary amines. Selectivity coefficients were used to express the degree of interaction, with experiments showing that these values remain constant over wide variations in resin, drug, and alkali metal concentrations. Rate studies demonstrated that both adsorption of drug onto the resin and elution from the resin are very rapid. The rapid elution rates, along with decreasing resin affinity for amine drugs above pH 6.0, indicate that the presence of polacrilin potassium in a dosage form should not affect total drug availability in the gastrointestinal tract.
High potency adsorbates of methapyrilene, dextromethorphan, ephedrine, and pseudoephedrine were prepared by column procedures using a polymethacrylic acid ion-exchange resin. Taste evaluation of the adsorbates showed a significant reduction in bitterness of the drugs. Coating the adsorbate particles with a 4:1 ethylcellulose-hydroxypropylmethylcellulose mixture reduced the bitterness further. Taste coverage was maintained after incorporation of the coated adsorbate into chewable tablets. In vitro release-rate studies showed immediate and complete drug elution from uncoated adsorbates. Release from coated adsorbates varied with the extent of coating. In vivo drug availability was demonstrated by LD50 tests in mice and rats and by a urinary excretion crossover study in humans.
The concentration of quinidine in plasma was measured in 12 healthy subjects during multiple administration of an enteric coated tablet (Systodin) and two sustained release preparations (Kinidin Duretter and Kinilentin). In a second study, involving another 12 subjects, the enteric coated tablet and the most widely used sustained release preparation (Kinidin Duretter) were compared with plain uncoated quinidine sulphate tablets in order to calculate the relative bioavailability of the formulations used for maintenance therapy. The largest area under the plasma concentration-time curve (AUC12h) during a dosage interval (12 hours) was obtained with the plain tablets and with the enteric coated formulation. The variation of the plasma concentrations during the dosage interval was not larger with the enteric coated tablets than with the sustained release preparations. The time of appearance of peak concentration after administration was longer and more variable with the enteric coated tablets. In relation to the plain quinidine tablets, the bioavailability of Systodin and Kinidin Duretter was 96% and 84%, respectively. In 21 out of 24 crossover experiments with Kinidin Duretter and Systodin the AUC12h was larger with the latter formulation. Enteric coating appears to be a simple and reliable means of achieving delayed absorption and stable quinidine plasma levels during maintenance therapy.
In order to prepare fine granules of sparfloxacin (SPFX), a new quinolone anti-bacterial drug that shows masking of the bitter taste of SPFX and dissolutes at a rapid rate, various film-coated fine granules containing 20% SPFX and 0-52% low-substituted hydroxypropylcellulose(L-HPC) in the cores, were prepared by a spray method. Mixtures of ethylcellulose (EC), hydroxypropylmethylcellulose (HPMC), titanium dioxide and sucrose stearate in weight ratios of X:Y:2:1 (X + Y = 6) were used as film materials. The degree of masking of the bitter taste by water-insoluble film, mainly consisting of EC and HPMC, increased by increasing the content ratio of EC to HPMC and the amount of films, but was also slightly affected by the amount of L-HPC in the cores, which were coated with either EC or EC/HPMC (4/2). On the other hand, the dissolution rate increased with an increased amount of L-HPC in the cores and with a decreasing ratio of EC to HPMC in the films. Increasing the amount of L-HPC in the cores, which induced a considerable expansion of the fine granules owing to their taking up of water from the dissolution medium, resulted in bursting of the film after a short lag time. The bioavailability of the film-coated fine granules containing 20% SPFX and 52% L-HPC in the cores and 10% EC/HPMC (4/2) in the coating film, which masked the bitter taste of SPFX and showed the optimal release characteristics, was equivalent to that of conventional tablets containing 100 mg SPFX in beagle dogs.
Taste cells use a wide variety of mechanisms for transduction. Ionic stimuli, such as salts and acids, interact directly with ion channels to depolarize taste cells. More complex stimuli, such as sugars and amino acids, utilize apically located receptors for transduction. Recent molecular biological results suggest that the metabotropic glutamate receptor mGluR4 may function in glutamate taste transduction. New biochemical studies have identified a bitter-responsive receptor that activates gustducin. Unexpected results with knockout mice suggest that gustducin may be directly involved in both bitter and sweet transduction. Electrophysiological experiments indicate that both inositol trisphosphate and cyclic nucleotides function in both bitter and sweet transduction events.
Chloroquine diphosphate, a highly water-soluble drug, was encapsulated by using a non-solvent addition coarcevation method. The coating material employed was Eudragit RS100. The liquid manufacturing vehicle was tetrahydrofuran (THF) while the non-solvent liquid was cyclohexane. Polyisobutylene (PIB) was used as an anti-aggregating agent. Particle size as well as shape evaluation was performed. Total drug content, in vitro drug release (from the microcapsules) as well as tasting test experiments were performed. The release studies on the microcapsules revealed an in vitro prolonged release effect while at the same time the bitter taste of the drug appeared to have been considerably masked by this method.
Cefuroxime axetil (CA) was encapsulated in pH-sensitive acrylic microspheres in order to formulate a suspension dosage form. Using this microencapsulated form it was expected to prevent leaching of the drug from the microspheres into the suspension medium and to assure the release of the drug in the first part of the intestine, thus avoiding changes to its bioavailability. For this purpose, CA was microencapsulated within several types of acrylic polymers by the solvent evaporation and the solvent extraction techniques. The acrylic polymers selected were: Eudragit E (positively charged and soluble at pH 5), Eudragit L-55 (negatively charged and soluble at pH > 5.5) and Eudragit RL (neutral, insoluble, but readily permeable). The influence of the polymer electrical charge on the stability and in vitro release of CA was investigated. Though Eudragit E microspheres presented good morphological characteristics and dissolution behaviour, the analysis of the stability of CA in the presence of Eudragit E by HPLC, indicated a negative interaction between both compounds. However, formulations made of Eudragit L-55 and RL in the ratios 100:0 and 90:10 were adequate in terms of the stability of the encapsulated CA. The dissolution studies showed a critical pH between 5.2 and 6.0, which allowed the complete release of CA in a short period. Furthermore, these polymer microspheres were shown to be efficient in masking the taste of CA.
To improve the bioavailability and taste of fast-disintegrating tablet (FD tablet) containing nicorandil-loaded particles.
A FD tablet containing nicorandil-loaded particles with 1%-4% croscarmellose sodium in addition of D-mannitol and lactose (9:1) was prepared and the dissolution and absorption characteristics were examined, in comparison with FD tablet and commercial tablets of nicorandil. In vivo absorption of nicorandil from FD tablet was evaluated in beagle dogs.
The disintegration time of FD tablets containing 1% croscarmellose sodium with 6 mm and 10 mm in diameter were about 12 and 23 seconds, respectively. When nicorandil-loaded particles consist of myristyl alcohol and stearyl alcohol were put in FD tablet, nicorandil release from FD tablet continued until 6 h while nicorandil release from Sigmart and FD tablet containing nicorandil crystals finished within 5 min. In vivo absorption of nicorandil from Sigmart and FD tablet containing nicorandil crystals was very similar after oral administration in beagle dogs and no statistic difference in AUC, Tmax, Cmax was observed between these tablets. However pharmacokinetics parameters of nicorandil after oral administration of FD tablet containing nicorandil-loaded particles showed that nicorandil was delivered into the body at a suitable absorption rate with similar AUC, delayed Tmax and lower Cmax.
The reports suggest that the modification of properties of myristyl alcohol and stearyl alcohol released from the drug-loaded particles system would lead to more acceptable bioavailability of the system. However, The formulation of particles and may have a masking effect against the bitter taste and irritation of the drug.
Sodium benzoate is used as a therapeutic agent in the treatment of some rare disorders that predominantly affect children. In preliminary investigations, liquid and semi-solid formulations of sodium benzoate failed because children refuse the oral uptake due to the bad taste of the drug. Recently developed microcapsules with macrogol as a hydrophilic binder raise concern in high-dose treatment regimens because acceptable daily intake limits are exceeded. A novel microcapsule formulation was developed consisting of a lipophilic core with high sodium benzoate load and a saliva-resistant coating. A new powder quality of saturated triglycerides from plant origin was introduced which complies with the Ph. Eur. monograph 'Hard fat'. Sodium benzoate and the triglyceride were mixed and directly extruded at room temperature. The extrudates were spheronized and coated in a fluidized-bed process. The resulting coated granules are small-sized microcapsules and taste neutrally. They can be mixed with food before administration. As the amount of released sodium benzoate is negligible within the first minutes, children do not recognize the bad taste and accept the medication. Recently, sodium benzoate in this novel formulation has been designated by the European Community as an orphan drug in the treatment of non-ketotic hyperglycinemia.
High doses of sodium benzoate are applied in the treatment of some rare metabolic disorders. In most cases children are affected who often refuse the oral uptake of sodium benzoate as a powder or in solution due to its bad taste. Therefore, small-sized, saliva-resistant microcapsules have been developed containing high doses of the drug substance. Granules were produced by roller compacting of sodium benzoate powder without any additives, by solvent-free cold extrusion and hot-melt extrusion adding poly(ethylene glycol)s of different grades. The granules with a diameter of less than 1 mm were film-coated by an ethanolic solution of Eudragit E 100. The microcapsules from hot-melt extrusion containing 25% Macrogol 4000 were most stable during the coating process and showed the highest yields. Sodium benzoate is completely released from the microcapsules within 9 min into 0.1 N HCl and 0.01 N HCl whereas dissolution into buffer pH 6.8 is different in the initial phase and completed after 14 min. The bad taste of sodium benzoate is not recognized in the buccal space for at least 5 min. The microcapsules are stable during storage for at least 6 months.
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