Achieving a robust drug release from extended release tablets using an integrated continuous mixing and direct compression line

Abstract

In the present work the viability of integrated continuous mixing and compression processes for manufacturing of extended release (ER) matrix tablets was investigated in terms of dissolution behavior. The purpose was also to evaluate the combined effect of processing variables and compositional variables on the release robustness. The continuous process was provoked by a challenging formulation design, including variable powder characteristics and compositions of high and low amount of poorly soluble and poorly flowing drug substance (ibuprofen). Additionally a relatively low amount of two different ER matrix former grades (standard granulation grade CR and direct compression grade DC2 of hydroxypropyl methylcellulose, HPMC) was used to challenge the system. Robust ibuprofen release was obtained faster when HPMC CR was used. However, robust release was also achieved when using HPMC DC2 at high ibuprofen content, even though it took slightly longer time to reach the steady state of the process. Due to its poor flow properties, HPMC CR would be very challenging to use in traditional direct compression. The results showed that by using continuous processing it is possible to manufacture and achieve robust performance of compositions that would not be possible with traditional batch processing due to for instance poorly flowability.

Keywords: Continuous direct compression; Continuous mixing; Dissolution; Extended release; Hydroxypropyl methylcellulose; Percolation; Robust drug release.