(298f) Determination of Flow and Compressibility Properties of Pharmaceutical Powders: Effect of Fines and High Drug Loading

Control of the particle size distribution (PSD) of incoming powders to a compaction process stream is difficult to manage in the pharmaceutical industry. When combined with a difficult to process active pharmaceutical ingredient (API) at a high loading, the effective processing into tablet form is made even more complicated. Understanding flow performance and influencing trends on compaction will go a long way to identifying potential mechanisms to maintain robust control of the tableting process. In this study, the effect of high loading and PSD variation of ibuprofen, a cohesive and poor flowing API, were investigated by assessing the powder flow performance and compaction into oral solid dosage forms (OSD). Increasing the number of large ibuprofen particles produced a more free-flowing blend as indicated by a reduced compressibility (CPS). However, the flow rate index indicated these blends were more sensitive to changes in flow rate. Increasing the fines content in the API fraction correlated with increased tensile strength and disintegration time in final tablets. By analysing the flow and compressibility properties an understanding of the physical interactions in both the blend and OSD were established. Adhesion mechanisms between fine and larger particles, and the particle shape had an influence on the processability of the blends. Determining the effective responses of key quality indicators of powder blend behaviour to PSD variation at critical process points, and combining this knowledge with in-line monitoring and system analysis, through application of process analytical tools (PAT), are control strategies which can be applied in a continuous manufacturing line.