(339g) Simultaneous Particle Size Reduction and Surface Modification to Enhance Flowability of APIs

In this work simultaneous size reduction and surface coating is considered in order to increase the dissolution of drugs while maintaining their flowability. This is accomplished by coating nano-sized, silica guest particles on the surface of API particles, while they are reduced in size through Fluid Energy Mill (FEM). Two types of APIs are used: acetaminophen and ibuprofen. Two types of nano-silica are applied. One is hydrophilic silica M5-P, another one is hydrophobic silica R-972 pharma. Both are pharma grade excipients. Particle size distributions before and after the FEM process are investigated. The results show that with the increase of grinding pressure, the mean particle size decreases. For ibuprofen, before the process the mean particle size is about 100 microns, after the process the mean particle size decreases to about 10 microns. Angle of repose in various conditions is tested, indicating acceptable flow for such fine particles. Ibuprofen with 1.0 wt % of silica M5-P coated show the best flowability. SEM images confirmed the extent of surface modification with silica.

Another objective of this work is to produce high content API with good dispersion and flowability, which may be suitable for inhalation application. Hydrophobic biodegradable material (such as L-leucine) is applied instead of using nano-sized particles to modify the particle surface.

Proposed approach results in simultaneous particle size reduction and surface modification. The particle size is reduced and at the same time the flowability of powders is improved. Powders in size range 1-10 microns are produced with high API content (>95 %), having good dispersion and flowability without use of nano-particles.