Application of an adsorption isotherm to explain incomplete drug release from ordered mesoporous silica materials under supersaturating conditions

Abstract

Ordered mesoporous silica (OMS) materials have received significant attention in recent years for use as effective supersaturating oral delivery systems for poorly water-soluble drugs. Whilst OMS materials are indeed capable of generating drug supersaturation, previous research has demonstrated incomplete drug release to always be a feature of OMS formulations. A dynamic adsorption equilibrium between drug adsorbed to OMS and free drug in solution has been hypothesized as the underlying cause of incomplete release. Therefore, the aim of this study was to characterize the adsorption of hydrophobic ritonavir (as a model poorly water-soluble drug) to OMS from supersaturated solutions. Importantly, this study represents the first report of drug adsorption by mesoporous materials under supersaturating conditions. Extensive adsorption of ritonavir from solution by mesoporous SBA-15 silica was observed for the concentration range spanning below the crystalline solubility to slightly above the amorphous solubility of ritonavir, with the extent of drug adsorption increasing with the extent of supersaturation. The Brunauer-Emmett-Teller (BET) isotherm equation (adapted for solution phase adsorption) provided the best fit to the adsorption data (R2 = 0.94) and afforded important mechanistic insights. Hydrogen bonding between ritonavir and SBA-15 surface silanols drives adsorption from subsaturated/saturated solutions, whereas the increased thermodynamic activity of the drug drives adsorption from supersaturated solutions. These observations account for the incomplete release of drug molecules from OMS materials under both dilute and supersaturating conditions. In summary, the high surface free energy of OMS materials and high reactivity of surface silanol moieties leads to incomplete drug release under a wide range of dissolution conditions. The findings described herein have significant implications for the application of OMS materials for oral drug delivery, especially for poorly water-soluble drugs which rely on supersaturation for adequate exposure in vivo.