Preparation and Evaluation of Orally Disintegrating Tablets Containing Vitamin E as a Model Fat-Soluble Drug

摘要

The purpose of the present study was to develop orally disintegrating tablets (ODTs) containing fat-soluble drugs that disintegrate rapidly while having appropriate tablet strength. We chose vitamin E (YE) as a model drug; d-alpha-tocopheryl acetate, as the oily YE (VE-OI), and d-alpha-tocopheryl acid succinate, as the powder YE (VE-PO), were used. The oily YE was added directly to ODTs (YE-OI ODTs) and also used for the preparation of two types of YE granule, i.e., granules prepared using adsorption to calcium silicate (YE-FL granules) and granules prepared using spray-drying with gelatin (YE-SD granules); each type of granule was added to ODTs (YE-FL ODTs and VE-SD ODTs). Powder YE was added directly to ODTs (YE-PO ODTs). Various YE ODTs were prepared using these four additional methods with varying amounts of YE per tablet and were evaluated with respect to their manufacturability, physicochemical characteristics, and stability. It was demonstrated that a tablet porosity of 30% to 35% and tensile strength of 7kg/cm(2) or greater are required to provide YE ODTs with rapid disintegration and appropriate tablet strength, and that YE-SD granules and powder VE are suitable forms of YE to be added. When stability tests of YE-SD ODTs and VE-PO ODTs were performed, VE-PO ODTs exhibited prolongation of disintegration time and increased tensile strength, whereas YE-SD ODTs showed none of these changes. These changes were thought to be attributable to a decrease in the pore size of YE-PO ODTs resulting from the softening and migration of powder YE under hot storage conditions.