(602d) Predictive Approach to Estimate Viability of Dry Coating for CQA Enhancement of Pharmaceutical Powders

Loose powder packing and powder flowability are both important critical quality attributes (CQAs) to consider in relation to pharmaceutical tablet manufacturing. Such CQAs impact the efficiency of various unit operations such as feeding, blending, conveying, and compaction. Fine pharmaceutical powders (<100 µm) often have inadequate packing and flow, due to high cohesion among the individual particles. In this work, ability to predictively enhance such properties, specifically, the bulk density, expressed by powder packing porosity, and flowability, expressed through flow function coefficient (FFC) after nano-silica dry coating, was examined. This was done through computation of the granular Bond number and cohesion force estimated via multi-asperity contact model for twenty different pharmaceutical powders. Despite variations in size (10–225 µm), particle size distribution, aspect ratios (1-3.5), material density, and dispersive surface energy, the bulk density and FFC improvements after dry coating followed predictive trends. However, there were a few outliers for the porosity prediction model, Microcrystalline Cellulose (MCC) excipients were outliers, for which their behavior was assessed through analysis of their shape, surface morphology and specific surface areas (SSA). Consequently, approaches to improve the multi-asperity models for better estimation of the Bond number were examined. The work also developed guidelines for what class of powder materials may provide more accurate prediction. The investigation included experimental results of optimum nano-silica amount, and trends of CQA improvement after dry coating, and comparison of nano-silica glidants. Most impressively, the bulk density and FFC enhancement were as high as 70-90 % for finer, more cohesive powders, indicating that dry coating works well for the powders for which it is needed the most. This ability to estimate the expected enhancements after dry coating a priori can guide decision making regarding whether or not dry coating is necessary or would be beneficial.