Physical state and dissolution of ibuprofen formulated by co-spray drying with mesoporous silica: Effect of pore and particle size

Abstract

A model poorly aqueous-soluble drug, ibuprofen (IBU), was co-spray dried with mesoporous silica materials having different pore sizes and particle sizes for dissolution enhancement. Drug molecules were entrapped inside the mesoporous channels at a high drug loading of 50:50 (w/w). The pore sizes were found to affect the physical state and particle size of IBU in mesoporous structures, which influenced the dissolution profiles. When IBU was co-spray dried with MCM-41 and SBA-15 with pore size smaller than 10 nm, amorphous state of IBU was obtained due to nano space confinement. In contrast, nanocrystals were obtained when ibuprofen was co-spray dried with large pore SBA-15-LP with pore size above 20 nm. The physical state of ibuprofen played a key role in affecting the dissolution of IBU from the solid dispersion. IBU in the amorphous state exhibited a higher dissolution rate than nanocrystalline IBU, even though the larger pore size could facilitate diffusion from the host matrix. The particle size of mesoporous silica showed a less pronounced effect on the dissolution of IBU. Thus, the amorphous/nanocrystalline state of ibuprofen was the most important influence on drug dissolution followed by the diffusion kinetics, particle size of IBU and path length from host matrix to dissolution medium. © 2011 Elsevier B.V. All rights reserved.