Design and Optimization of Taste Masking Process for Bitter Tasting Drug

Abstract

Orally disintegrating tablet is an attractive and preferred dosage form in which the drug disintegrates or dissolves in the buccal cavity without the need of water. This patient-centric drug delivery system is designed to increase patient compliance across several patient population, especially geriatric and pediatrics who are most likely to suffer from dysphagia that is swallowing difficulties. This is particularly significant as the world’s population continues to grow, and people are living longer. These formulations are considered easier to administer compared to classic dosage forms, like swallowable tablets and capsules, since there is no need for water. When disintegrated in the mouth (with just saliva), they offer faster onset of action, better absorption and improved bioavailability making them attractive dosage formats for patients and manufacturers. Designing these dosage forms has been limited by the unpleasant taste of the drug substance. Two such unpleasant tasting drugs evaluate for the research purpose were Levocetirizine Dihydrochloride and Pioglitazone Hydrochloride. The first one “Levocetirizine Dihydrochloride”, is an antihistaminic drug, which is white, crystalline, water-soluble powder used for the relief of symptoms associated with allergic rhinitis in adults and children 6 years and above. The taste of levocetirizine dihydrochloride is generally bitter. And the another one, “Pioglitazone Hydrochloride” is the hydrochloride salt of an orally active thiazolidinedione with antidiabetic properties and potential antineoplastic activity. It is odorless, white crystalline powder and practically insoluble in water (BCS II drug). The taste of pioglitazone hydrochloride is relatively unpleasant. The objective of the study was to develop orally disintegrating tablet of these two unpleasant tasting drug molecules by applying polymeric layer over drug particles and using these coated particles to formulate orally disintegrating tablet. The study design for masking unpleasant taste of the drug involves use of pH-independent water insoluble polymeric dispersion of Ethylcellulose “Surelease E-7019040” in combination with pH-independent water-soluble polymeric dispersion of Hypromellose based “Opadry YS-1-19025-A” as a pore former in different ratios to mask bitter taste of the drug without impacting immediate drug release characteristics of the formulation. To determine effective masking of bitterness of the drug, in-vitro and in-vivo taste evaluation were performed. Uncoated and coated drug substances and prepared tablets were evaluated for physico-chemical properties such as flow, compression, Fourier Transform Infrared absorption spectra, Powder X-ray Diffraction, Scanning Electron Microscopy, in-vitro dissolution, and in-vitro disintegration properties. For designing orally disintegrating tablets, three different diluents (microcrystalline cellulose, mannitol, lactose monohydrate) and three different concentrations of super disintegrant (crospovidone) were taken into consideration. Result of the study indicated no change in polymeric form of drug post taste masking application for both the drug molecules, however, significant retardation in drug release at initial time point was achieved to avoid bitter sensation in the mouth and possibly during its transit through esophageal tract followed by complete drug release in stomach. Orally disintegrating tablet of levocetirizine dihydrochloride and pioglitazone hydrochloride designed with mannitol as a diluent and highest concentration of crospovidone (6%) as a super disintegrant resulted in a desired palatability as indicated by rating given by healthy volunteers during in-vivo taste evaluation studies. The study concludes, easy to use and simple technique to mask taste of unpleasant drug followed designing palatable pharmaceutical dosage form with desired formulation properties.