Reviewing the Impact of Powder Cohesion on Continuous Direct Compression (CDC) Performance

The pharmaceutical industry is undergoing a paradigm shift towards continuous processing from batch, where continuous direct compression (CDC) is considered to offer the most straightforward implementation amongst powder processes due to the relatively low number of unit operations or handling steps. Due to the nature of continuous processing, the bulk properties of the formulation will require sufficient flowability and tabletability in order to be processed and transported effectively to and from each unit operation. Powder cohesion presents one of the greatest obstacles to the CDC process as it inhibits powder flow. As a result, there have been many studies investigating potential manners in which to overcome the effects of cohesion with, to date, little consideration of how these controls may affect downstream unit operations. The aim of this literature review is to explore and consolidate this literature, considering the impact of powder cohesion and cohesion control measures on the three-unit operations of the CDC process (feeding, mixing, and tabletting). This review will also cover the consequences of implementing such control measures whilst highlighting subject matter which could be of value for future research to better understand how to manage cohesive powders for CDC manufacture.