Data-driven modeling approach to investigate the tableting properties of three powder blends for pharmaceutical product development

The manufacturing process of pharmaceutical tablets involves feeding a powder formulation into a die followed by compaction using rigid punches. The die filling step is part of a larger tableting process which is usually performed using the multiple station rotary press and it has a major impact on the quality, uniformity and mechanical properties of the tablets produced. In this study, the effect of the main compression settings of the rotary press on the final tablet quality is analyzed for three different blends by exploiting multivariate statistical techniques, with a particular focus on weight consistency and uniformity, which are the most important quality parameters in die filling. It results that, while some settings have the same effect on all the considered blends (e.g., feed frame speed in increasing mean weight or overfill in decreasing weight variability), some others affect each blend in different ways. This may be related to the properties of the powder itself, in particular its flowability, which are known to be related to the operating conditions of the rotary press in determining die filling performance. In particular, it has been found that tablets made from more flowable powders are characterized by lower weight variability. The effect of the feed frame on the lubrication state of the blends is also evaluated, as its mechanical action can cause particle friction and over lubrication, resulting in lower tablet strength and slower dissolution. By comparing the data collected on the compactor simulator for both powder samples and samples with known lubrication, it is concluded that the feed frame only has a meaningful effect on powder lubrication above a certain feed frame speed.