The purpose of the present study was to develop orally disintegrating tablets (ODTs) containing fatsoluble drugs that disintegrate rapidly while having appropriate tablet strength. We chose vitamin E (VE) as a model drug; d-α-tocopheryl acetate, as the oily VE (VE-OI), and d-α-tocopheryl acid succinate, as the powder VE (VE-PO), were used. The oily VE was added directly to ODTs (VE-OI ODTs) and also used for the preparation of two types of VE granule, i.e., granules prepared using adsorption to calcium silicate (VE-FL granules) and granules prepared using spray-drying with gelatin (VE-SD granules); each type of granule was added to ODTs (VE-FL ODTs and VE-SD ODTs). Powder VE was added directly to ODTs (VE-PO ODTs). Various VE ODTs were prepared using these four additional methods with varying amounts of VE 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 7 kg/cm 2 or greater are required to provide VE ODTs with rapid disintegration and appropriate tablet strength, and that VE-SD granules and powder VE are suitable forms of VE to be added. When stability tests of VE-SD ODTs and VE-PO ODTs were performed, VE-PO ODTs exhibited prolongation of disintegration time and increased tensile strength, whereas VE-SD ODTs showed none of these changes. These changes were thought to be attributable to a decrease in the pore size of VE-PO ODTs resulting from the softening and migration of powder VE under hot storage conditions. Key words orally disintegrating tablet; fat-soluble drug; vitamin E; disintegration; tensile strength; porosity Most pharmaceutical dosage forms for oral administration are developed for drug delivery after swallowing. In particular, tablets and capsules are the most common oral solid dosage forms, because they are convenient to carry, the duration of action of the contained drugs can be controlled, 1) and their taste or smell can be improved.
2)However, many geriatric and pediatric patients often have difficulties swallowing conventional tablets or capsules.3) It is estimated that 50% of the population experiences this problem, which results in a high prevalence of non-compliance and ineffective therapy. 4,5) To overcome this issue, a variety of pharmaceutical studies have been conducted to develop new dosage forms. Among the dosage forms developed to facilitate ease of medication, the orally disintegrating tablet (ODT) is one of the most widely employed in commercial products.
6)Numerous studies have therefore been performed on the various compositions of and manufacturing methods for ODTs. For example, ODTs can be prepared by several manufacturing methods, e.g., lyophilization, 7) granulation, 8) the cotton candy process, 9) and phase transition of sugar alcohols by direct compression. 10,11) The oily type of fat-soluble drugs have generally been produced and marketed commercially in soft capsule form, 12) though some prescription and over-the-counter d...