(76d) Using Inverse Gas Chromatography to Assess Passivation of High Surface Energy Sites of Milled Pharmaceutical Crystals Via Dry Coating of Nano-Silica

In this work, we examine the influence of simultaneous micronization and surface modification via dry coating of nano-silica particles on the surface energy of ibuprofen crystals milled down to different sizes to be able to explain higher surface energy of milled ibuprofen and mitigation thereof via dry coating. Fluid energy mill was used to micronize ibuprofen particles to sizes from 5 to 30 µm with or without simultaneous dry coating with nano silica. Bulk powder properties such as bulk density, compressibility, unconfined yield strength were characterized using Freeman FT4 rheometer, and powder dispersibility was measured using Rodos/Helps system by Sympatec. Surface properties were characterized using the Surface Energy Analyzer, via Inverse Gas Chromatography (IGC) to be able to explain the bulk flow improvement due to dry coating.

As received, uncoated, micronized ibuprofen samples show an increase of dispersive surface energy (from 40.7 to 54.4 mJ/m²) as the particle size decreases with increasing milling intensity. On the other hand, dry coated milled ibuprofen powders show an overall decrease in the dispersive surface energy. The detailed surface energy maps reveal that pure micronized ibuprofen surface is highly heterogeneous, while dry coating reduces the heterogeneity. All of the measured bulk powder properties showed an improvement due to dry coating. 

Overall, it was found that improved powder flow and packing characteristics may be obtained when milling includes simultaneous surface modification via dry coating of nano-silica, thus eliminating disadvantages of micronization. These improvements are attributed to decreased cohesion indicated by reduced dispersive surface energy. Increased surface energy, hence cohesion for ordinary milled ibuprofen may be due to creation of high energy sites during milling, where as the detailed surface energy measurements indicate that dry coating with nano-particles quench the high energy sites and making ibuprofen surface less heterogeneous and having reduced surface energy comparable to that of the nano-particles used for dry coating.