Formulation Design of Taste-Masked Particles, Including Famotidine, for an Oral Fast-Disintegrating Dosage Form

Abstract

Many elderly patients often have difficulty swallowing some of the dosage forms (tablets, capsules, and powders) currently used. For this reason, the development of an appropriate dosage form for elderly patients is most desirable. Since the late 1980s, many companies have developed fastdisintegrating dosage forms that disintegrate easily in the mouth and can be taken without water. Cardinal Health marketed a fast-disintegrating, freeze-dried porous wafer known as Zydis 1,2) and CIMA also marketed an effervescent tablet known as OraSolve.3) Eisai developed the EMP tablet, 4) and Ethypharm developed Flashtab.5) A new fast-disintegrating tablet consisting of high-and low-compressibility saccharides was reported in a previous study. 6) Although famotidine was used as a model drug for the new fast-disintegrating tablet, it had an unpleasant taste. In fact, most of the fast-disintegrating technologies described above were not applied to bitter-tasting drugs. Consequently, in this study, attempts have been made to produce a taste-masked, fast-disintegrating tablet using famotidine as a model drug.Various taste-masking technologies, such as the addition of sweeteners and flavors, coating with water insoluble materials, 7) creating a wax matrix by spray congealing, 8) adsorption to ion-exchange resin, 9,10) and complexing with cyclodextrins 11) had been investigated. Water insoluble polymer coating technology was widely employed to control the initial dissolution rate and to suppress the bitter taste. Famotidine bulk powder was coated in a fluidized-bed granulator in an attempt to suppress the bitter taste, but this was not successful. Because the reproducibility of coating operation was not achieved due to the poor flowability of famotidine powder. Therefore, the spray-drying method was selected as an alternative to the powder coating method.The objectives of this study were to determine the optimum formula and manufacturing conditions for producing taste-masked particles using the spray-drying method that could be applied to a fast-disintegrating tablet. If successful, this would result in a novel, taste-masked, fast-disintegrating tablet. ExperimentalMaterials The D-mannitol (Mitsubishi Shoji Foodtech, brand name: Mannit P), maltose (Hayashibara, brand name: Sanmalt), Aquacoat ECD30 (Ethylcellulose Aqueous Dispersion, FMC Corporation), Eudragit NE30D (Ethyl Acrylate Methyl Methacrylate Copolymer Dispersion, Röhm GmbH & Co., KG), triacetin (Yuki Gosei Kogyo), and calcium stearate (Nippon Oil & Fats) were used in this study. Famotidine (Astellas Pharma Inc., JP standard) was used as the model drug.Determination of Bitterness Threshold After mixing famotidine bulk powder and placebo granules consisting of mannitol granulated with 5% maltose in a fluidized-bed granulator, a tablet was prepared by compressing in an hydraulic press (weight of tablet: 170 mg, diameter of tablet: 8.5 mm). The concentrations of famotidine used were 0.5, 1, 2, and 5 mg per tablet. Sensory testing was conducted as follows: each volunteer washed...

Novel taste-masked orally disintegrating tablets for a highly soluble drug with an extremely bitter taste: design rationale and evaluation

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