An In Vitro Dissolution Method for Testing Extended-Release Tablets Under Mechanical Compression and Sample Friction

Abstract

The release and dissolution of an active pharmaceutical ingredient (API) from the solid oral formulation into the gastrointestinal (GI) tract is critical for the drug's absorption into systemic circulation. Extended-release (ER) solid oral dosage forms are normally subjected to physical shear and grinding forces as well as pressure exerted by peristaltic movements when passing through the GI tract. The complex physical contraction and sample friction exerted by the GI tract are not simulated well by compendial dissolution methods. These limitations render traditional in vitro dissolution testing unable to discriminate and predict a product's in vivo performance. The objective of this study was to develop a dissolution method that better simulates the GI environment that products are subject to when taken by patients. A newly designed Mechanical Apparatus under GI Conditions (MAGIC) was assembled with a dissolution platform and mechanical capabilities to allow in vitro dissolution testing under sample contractions and friction. The dissolution platform, with medium flow-through configuration, was manufactured by 3D printing. A 60 mg polymer matrix-based ER nifedipine product was tested. To simulate GI physiological conditions during the dissolution testing, the flow rate of the medium, and a combination of mechanical compression with rotation induced sample friction at various rotation frequencies were explored. The polymer matrix-based nifedipine ER formulation used here failed its controlled release functionality in the simulated GI environment under mechanical compression and sample friction. The results showed that the MAGIC system, with flow-through configuration under compression and sample friction, has advantages over compendial methods in testing ER solid oral formulations.

Keywords: Critical quality attributes (CQAs); Extended-release (ER); Gastrointestinal (GI) condition; In vitro dissolution testing; Mechanical apparatus under GI condition (MAGIC) system; Medium flow-through configuration; Simulated GI compression and friction.