Multi-faceted characterization of pharmaceutical powders to discern the influence of surface modification

Abstract

The present work is a comprehensive investigation of the flow, packing, and aeratibility behavior and discerning the rank order of several Active Pharmaceutical Ingredients (API), with or without surface modification, as well as excipients with different particle sizes and shapes. Surface modification of the API powders (various size grades of acetaminophen, ascorbic acid and ibuprofen) was conducted in a magnetically assisted impaction coater (MAIC), a well-established material sparing device. Powder characterization was done using various conventional and novel powder characterization techniques to measure properties such as, angle of repose, flow index, aerated, tapped and conditioned bulk densities, Housner ratio, Carr index, flow function coefficient (FFC), cohesivity and aeratibility. The comparative results show that surface modification improves flow, packing and aeratibility of powders with respect to corresponding as received powders, and in many cases, dry coated API powders exhibit properties as good as or better than similar sized excipients. The measured properties from different instruments were plotted through several illustrative phase maps with intent to develop a better visualization of the property improvements via dry coating. It was seen in the phase map of FFC vs. conditioned bulk density that it was easy to visualize a clear change in flow regimes after surface modification. For example, surface modified fine API powders show a shift from highly cohesive region (FFC < 2) to easy flow region (4 < FFC < 10) or free flow region (FFC > 10) along with an increase in conditioned bulk density (< 0.4 g/ml to > 0.5 g/ml). The use of the proposed phase map in developing manufacturing feasibility guidelines is also proposed.