(583d) Particle Engineering Via Dry Coating of Micronized API Powders for Improved Dissolution of Directly Compacted Tablets with High Drug Loading

Han, X., New Jersey Institute of Technology

Our recent study showed that simultaneous micronization and surface modification through fluid energy milling (FEM), a continuous process, can improve both the flow and dissolution rate of the active pharmaceutical ingredient (API) powders. In this paper, the improved performance of direct compacted tablets with high drug loading of micronized dry coated API powders (20 µm) is examined. As a benchmark comparison, larger, 50 µm API powders dry coated without micronization using a continuous comil process are also considered. Blends with 30, 60 and 70% drug loading, containing API powders that are micronized or non-micronized and dry coated or uncoated are prepared and evaluated. The results show that the blends containing dry coated API powders, even micronized ones, have excellent flowability and high bulk density, which are required for direct compaction. In contrast, blends containing uncoated APIs have poor flow and lower bulk densities. As the drug loading increases, the difference between dry coated and uncoated blends is more pronounced, which is clearly illustrated through a bulk density-FFC phase map. Powder compressibility tests showed improved performance of dry coated powder blends, indicating a good potential for direct compaction. Consequently, tablets are formed through direct compaction for micronized API blends; tablets prepared from dry coated APIs exhibit superior compactibility and dissolution profiles, particularly for higher drug loadings. Dissolution time, t80, for 30 or 60 % drug loaded tablets from 20 µm dry coated ibuprofen, is well under 5 min, illustrating the advantages of the dry coating during API micronization.