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

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. (C) 2011 Elsevier B.V. All rights reserved.