(383f) Simultaneous Micronization and Surface Modification as a Tool to Improve Flow and Dissolution of Pharmaceutical Powders

Dissolution improvement of poorly water soluble drugs is an active area of research, and it is generally expected that the micronization of Active Pharmaceutical Ingredient (API) particles would improve the dissolution rate of the API. However, micronization increases the cohesiveness of the API powder and gives rise to poor flowability, low bulk density and increased electrostatic. In addition, the micronized API particles tend to agglomerate heavily and expected increase in surface area leading to improved dissolution is not achieved in a solid dosage form. In this work, a novel approach is proposed to increase both the dissolution and flowablity of API powders. The process involves simultaneous micronization and surface modification of API by dry coating of nano-silica in a continuous mill.

Ibuprofen is considered as a model API which has been milled from 102 micron (as received) to 10 and 20 micron using different operating conditions of mill and the API is simultaneously coated with hydrophilic nano-silica. Resulting powder is characterized using laser diffraction (Rodos Helos), SEM, shear cell testing (Freeman FT4), angle of repose (Hosokawa powder tester), and vibrated packed density (VPD) to understand its flow and fluidization behavior. Dissolution profile of the powder is also tested using USP dissolution tester (via basket method). All the results were compared for as received Ibuprofen and milled Ibuprofen with and without any surface modification. The results show significant improvements in flow and dissolution properties when the micronization is done in conjunction with the surface modification. The surface modified, micronized powder shows significantly higher bulk densities, in some cases as much as doubling in value. These fine powders may be used in formulations that may be amenable for direct compression with high drug loading.