Role of Silica Intrawall Microporosity on Abiraterone Acetate Solubilization and In Vivo Oral Absorption

Abstract

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 m 2 /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 vivo C max , providing evidence for an association between silica microporosity and oral drug absorption.

The Anti-Obesity Effect of Porous Silica Is Dependent on Pore Nanostructure, Particle Size, and Surface Chemistry in an In Vitro Digestion Model

“…Unlike PSM, which are comprised of uniform microparticles (~2 µm in diameter) with random pore arrangements, SBA-15 forms large fiber-like aggregates with organized hexagonal pore structures that extend along the length of the individual rod-shaped particles (Figure 1). This unique porous nanostructure of SBA-15 presents a longer diffusional path length for digestion media (including enzymes, bile salts, lipids, etc.,) to be entrapped [11,23,24]. Here, it was evident that the rate and extent of fed state lipolysis was inhibited by each SBA-15 sample, when compared to the control, where lipase activity was reduced to 65-85% depending on the sample (Figure 5A,B).…”

The Influence of Blonanserin Supersaturation in Liquid and Silica Stabilised Self-Nanoemulsifying Drug Delivery Systems on In Vitro Solubilisation

“…This diminishing effect of super-SLH was attributed to a larger content of crystalline drug and less lipid available for solubilisation, highlighting that high drug loads do not necessarily correlate with improved performance, and a fine balance between drug load and performance exists. Further studies have investigated the application of super-SLH to abiraterone acetate, fenofibrate, simvastatin, and blonanserin (BLON), and have investigated the influence of different types of silica, silica geometry/microporosity, different LFCS LBF types, and liquid- vs. solid-state LBF [ 15 , 16 , 17 , 18 , 19 , 20 ].…”