(320d) Flow Improvement of Pharmaceutical Blends Via Surface Modification of Cohesive APIs

Surface modification of powders via dry coating of nano-particles or other flow aids has been shown to improve flow behavior of pharmaceutical materials. In this work, the behavior of pharmaceutical blends made of surface modified Active Pharmaceutical Ingredient (API) is examined. Surface modification of two grades of Acetaminophen (Coarse Acetaminophen, Micronized Acetaminophen) powders is carried out and the surface modified APIs are then used to prepare different blends with varying API loading (5 - 80%) including other additives such as disintegrants and lubricants, consistent with industrial practice. Three different types of blends (blends with dry coated API, blends with uncoated API with added nano-silica, and blends with uncoated API without nano-silica) are prepared to study the effects of surface modification on blends flowability. All three types of blends at various API loadings are characterized for flow and bulk density using various commercial and in-house powder testers; for example, Hosokawa Powder Tester, Freeman Powder Rheometer (FT4), Flodex, and Vibrated Packed Density device. The indices such as flow function coefficient (FFC), powder compressibility, angle of repose (AoR), bulk density, critical orifice diameter, etc., are measured and examined for the observable trends that relate with API loading and the surface modification. Blends prepared from surface modified API shows substantial improvement of bulk density, compressibility, FFC and AoR, etc. Improvements were observed over complete range of API loadings considered. For many cases, improvement in bulk density is significant enough to allow for direct compression without requiring granulation. Selected API blends are also used in compaction studies to examine the influence of surface modification.