(404f) A Systematic Study on Improving the Flowability of Poorly Flowing API By Dry Coating

Powder feeding being the first unit operation in a continuous manufacturing process in oral solid dose products, controls the content uniformity in the final product. Powders (i.e., Active Pharmaceutical Ingredients, APIs) with particle size below 50 μm exhibit poor flow, cohesive behavior, and adversely affect pharmaceutical operations such as feeding, mixing, and granulation. Silicification has thus been introduced to tackle this problem. In this method, nano silica is dispersed through the API using high shear stresses in a dry blending process. Due to the effect of the high shear stresses. Colloidal silica nanoparticles coat the API larger host particles breaking the large intermolecular cohesive forces that produce the high cohesiveness, low flowability behavior of bulk powders. This, in turn, improves the flowability of the API through the continuous system.

This study specifically concentrates on micronized Acetaminophen (mAPAP) used here as a model for challenging APIs to work with. mAPAP has a particle size of 12 μm (D50), and is known to exhibit high cohesion and very poorly flowability, This study aims to improve the flowability and bulk functions of the API blend, by silicifying it in a continuous process. The continuous operation needs to impart high enough shear strain to produce the de-agglomeration of the silicon dioxide nanoparticles, and for enough time to produce the desired dry coating of the host particles by the coating agent. A Comil was used to produce the high-shear conditions and thus dry coat the API and different strategies were put in place to increase the residence time of the material inside the high shear environment by decreasing the size and even by blocking the mesh in the co-mill. The method implemented in this study has helped improve the flow function coefficient of mAPAP from a very poor flowing to a good flowing material in a process that can be adapted in manufacturing environment and integrated into a semi-continuous process.