Influence of Formulation Factors, Process Parameters, and Selected Quality Attributes on Carvedilol Release from Roller-Compacted Hypromellose-Based Matrix Tablets.

The importance of roller compaction is recently increasing. This study evaluates the combined effects of formulation factors, process parameters, and selected quality attributes on drug release from roller-compacted hypromellose-based matrix tablets containing carvedilol as a model drug. The influence of selected factors was statistically assessed and good predictive models were developed for various time points of the release profile. The results show that the release profile is mostly affected by the particle size distribution of granules and roll speed. This indicates that the roller compaction process has a major impact on drug release, which is also formulation dependent. A higher d50 and lower d90 value of spatial filtering technique-based particle size distribution results, a lower roll speed, increased hypromellose content, using microcrystalline cellulose as a filler, and higher tablet hardness, resulted in a decrease in the drug release rate. On the other hand, the effect of the roll pressure, size of screen apertures, and d10 values on drug release was insignificant. The significance of the factors was further explained by granule shape, their porosity, and friability evaluation, and by compressibility and compactibility studies of compression mixtures. Additionally, the spatial filtering technique demonstrated to be a promising tool in controlling the roller compaction process.