Designing robust immediate release tablet formulations avoiding food effects for BCS class 3 drugs.

Food induced viscosity in the gastrointestinal tract is reported to reduce the bioavailability of tablets containing BCS class 3 drugs, mainly by retarding their disintegration and dissolution of the active pharmaceutical ingredient. The role of formulation factors in minimizing this negative food effect is largely unknown. Combinations of disintegrants were studied together with soluble and insoluble fillers and trospium chloride as model drug substance. Different batches of tablets were compressed at 10 KN and 30 KN, by incorporating different combinations of croscarmellose sodium (CSS), cross-linked polyvinylpolypyrrolidone (CPD) and sodium starch glycolate (SSG) at low level i.e, 2%+2% and high level i.e, 4%+4% of compressional weight, while taking lactose as a soluble filler and dibasic calcium phosphate (DCP) and microcrystalline cellulose (MCC) as insoluble fillers. Under low viscous conditions, disintegration of DCP based tablets was faster compared to lactose based tablets, but under high viscous conditions, simulating the effect of an ingested FDA meal, the disintegration behavior was reverted. Increased compressional force prolonged the disintegration of lactose and DCP based formulations under fasted conditions. However, when evaluated under food viscosity conditions, DCP based tablets compressed at higher force showed rapid disintegration while no effect of increased compressional force in lactose based tablets was observed. MCC based tablets in particular showed largely prolonged disintegration times in viscous media irrespective of the disintegrant type and levels investigated. Disintegrant combinations possessing wicking ability with minimum or no gelling were found to reduce disintegration times. The disintegrant combination of CPD + CCS was effective in reducing disintegration and enhancing dissolution besides not being affected by changes in compressional force and their total proportion in the tablet. In conclusion, it is recommended to evaluate formulations under increased viscosity conditions during the development phase of tablets with an objective to minimize the negative effect of food viscosity on disintegration and dissolution.