Formulation strategy towards minimizing viscosity mediated negative food effect on disintegration and dissolution of immediate release tablets

Abstract

Food induced viscosity can delay disintegration and subsequent release of API from solid dosage form which may lead to severe reduction in the bioavailability of BCS type III compounds. Formulations of such tablets need to be optimized in view of this postprandial viscosity factor. In this study, three super disintegrants, croscarmellose sodium (CCS), cross-linked polyvinylpolypyrrolidone (CPD), and sodium starch glycolate (SSG) were assessed for their efficiency under simulated fed state. Tablets containing these disintegrants were compressed at 10 and 30 KN, while taking lactose as a soluble filler. In addition to other compendial tests, disintegration force of these formulations was measured by texture analysis. Comparison of parameters derived from force – time curves revealed a direct relation of maximum disintegration force (F_max) and disintegration force development rate (DFDR) with compressional force in fasted state, whereas an inverse relationship of F_max and DFDR with compressional force was observed in fed state. The gelling tendency of disintegrants influenced the rate of release of API in simulated fed and fasted states when compressional force was changed. These observations recommend the evaluation of formulations in simulated fed state, in the development stage, with an objective of minimizing the negative impact of food induced viscosity on disintegration. Use of disintegrants that act without gelling or can counteract the effect of gelling is recommended for tablet formulations with reduced disintegration time (DT) and mean dissolution time (MDT) in fed state, respectively.

Keywords:

• Food-induced viscosity
• fed state
• disintegrants
• disintegration force
• disintegration
• dissolution
• texture analysis
• crospovidone
• sodium starch glycolate
• formulation development

Acknowledgements

We acknowledge the stipend provided by Higher Education Commission, Pakistan (HEC) through German Academic Exchange Services (DAAD) to Kamran Zaheer. This work serves as in kind contribution to the Innovative Medicines Initiative Joint Undertaking (http://www.imi.europa.eu) OrBiTo. The donation of trospium chloride by Dr. R. Pfleger, Bamberg, Germany is gratefully acknowledged.

Disclosure statement

No potential conflict of interest was reported by the authors.