The influence of milling of ribbons on selected granule quality attributes and carvedilol release from roller-compacted hypromellose-based matrix tablets

Abstract

Roller compaction is gaining importance in the pharmaceutical industry. This study evaluates the impact of ribbon milling conditions on properties of granules and compression mixtures and on drug release from hypromellose-based matrix tablets prepared with two different fillers. In the first part of the study, design of experiments (DoE) was utilized to investigate the effect of filler type (lactose and microcrystalline cellulose (MCC)), mill type (oscillating, conical and hammer mill), milling speed and the size of screen apertures on selected attributes (granule particle size distribution (PSD), porosity and shape), and on the compressibility and compactibility of compression mixtures. The effect of DoE factors and selected attributes on the release of carvedilol at different timepoints of the release profile (t = 1–7 h) was further assessed. The study showed that drug release was affected by filler type, mill type, and various attributes; however, their effect proved to be complex and strongly related to granule PSD. Therefore, this effect was minimized in the second part of the study, in which tablets containing the same amount of different particle size fractions of granules were prepared with different mills and fillers. The drug release profiles confirmed that drug release is mainly related to differences in filler type and granule PSD. However, they indicate that with lactose mill type also affected drug release, possibly due to differences identified in particle shape.