SBA-15 mesoporous silica (MPS) has been widely used in oral drug delivery; however, it has not been utilized for solidifying lipid-based formulations, and the impact of their characteristic intrawall microporosity remains largely unexplored. Here, we derive the impact of the MPS microporosity on the in vitro solubilization and in vivo oral pharmacokinetics of the prostate cancer drug abiraterone acetate (AbA) when coencapsulated along with medium chain lipids into the pores. AbA in lipid (at 80% equilibrium solubility) was imbibed within a range of MPS particles (with comparable morphology and mesoporous structure but contrasting microporosity ranging from 0-247 m2/g), and their solid-state properties were characterized. Drug solubilization studies during in vitro lipolysis revealed that microporosity was the key factor in facilitating AbA solubilization by increasing the surface area available for drug-lipid diffusion. Interestingly, microporosity hindered hydrolysis of AbA to its active metabolite, abiraterone (Ab), under simulated intestinal conditions. This unique relationship between microporosity and AbA/Ab aqueous solubilization behavior was hypothesized to have significant implications on the subsequent bioavailability of the active metabolite. In vivo oral pharmacokinetics studies in male Sprague-Dawley rats revealed that MPS with moderate microporosity attained the highest relative bioavailability, while poor in vitro-in vivo correlations (IVIVC) existed between in vitro drug solubilization during lipolysis and in vivo AUC. Despite this, a reasonable IVIVC was established between the in vitro solubilization and in vivoCmax, providing evidence for an association between silica microporosity and oral drug absorption.
Keywords: SBA-15; abiraterone acetate; lipid-based formulations; mesoporous silica; microporosity.