부산대학교 도서관

Abstract There is a current trend in pharmaceutical manufacturing to shift from traditional batch manufacture to continuous manufacturing. The purpose of this study was to test the ability of an integrated continuous direct compression (CDC) line, in relation to batch processing, to achieve consistent tablet quality over long processing periods for formulations with poor flow properties or with a tendency to segregate. The study design included four industrially relevant formulations with different segregation indices and flow properties induced through different grades of the Active Pharmaceutical Ingredient (API), paracetamol, and major filler as well as varying the amount of API. The performance metrics investigated were content, uniformity of content, tablet weight, and tablet strength. The overall process stability over time was significantly improved with the CDC line as compared to the batch process. For all the formulations with a high API content, the CDC line provided better or equal uniformity of content and tablet weight as compared to batch. The CDC line was especially efficient in providing a stable content and tablet weight for poorly flowing formulations containing the standard, cohesive, grade of API. The only formulation that performed better in the batch process was the formulation with a low API content. Thus, for this formulation, the batch process achieved lower variation in tablet content since maintaining a low feed rate for the API proved challenging in the CDC line. In addition, some of the API became stuck in the CDC line between feeding and tableting, most likely at the funnel in the mixer inlet, highlighting the need for properly designed interfaces between units. The insensitivity of the CDC line towards poor flow indicates that one could use direct compression at high drug load compositions of poorly flowing powder blends that could not be processed via batch manufacturing. Graphical abstract Unlabelled Image [ABSTRACT FROM AUTHOR]