Supersaturation Potential of Ordered Mesoporous Silica Delivery Systems. Part 1: Dissolution Performance and Drug Membrane Transport Rates.

Ordered mesoporous silica materials have shown great potential as oral drug delivery systems for poorly soluble drugs. However, the ability of these delivery systems to generate drug supersaturation has not been widely investigated, and the recently noted phenomenon of incomplete drug release is not well understood. Therefore, the aim of this study was to comprehensively evaluate the release of hydrophobic drug molecules into solution from ordered mesoporous silica, focusing on the extent and duration of drug supersaturation. The dissolution and supersaturation behavior of ritonavir, following loading into mesoporous SBA-15 silica particles, was investigated by undertaking simple in vitro dissolution studies in phosphate buffer pH 6.8 and fasted state simulated intestinal fluid, as well as membrane flux studies using a side-by-side diffusion cell apparatus. It was found that supersaturated ritonavir solutions were generated from ritonavir-loaded mesoporous SBA-15 particles; however, drug release was always incomplete, even under sink conditions. In addition, the percentage drug release was observed to decrease significantly as the theoretical supersaturation ratio and dose of ritonavir-loaded SBA-15 formulation increased. The data obtained suggest an equilibrium exists between drug adsorbed to the SBA-15 silica surface and free drug present in solution. The findings described herein are highly significant in aiding our understanding of ordered mesoporous silica as a supersaturating drug delivery system for bioavailability enhancement.