Enhancement of abiraterone acetate oral bioavailability by supersaturated-silica lipid hybrids

Abiraterone acetate (AbA) has an oral bioavailability of <10% due to its poor water solubility. Here we investigate the performance of silica-lipid hybrids (SLH) and supersaturated SLH (super-SLH) in improving oral bioavailability of AbA. Specifically, we investigate the influence of lipid type and AbA saturation level of the equilibrium solubility in the lipid (Seq), and explore in vitro-in vivo correlation (IVIVC). An oral pharmacokinetic study was conducted in fasted Sprague-Dawley rats. Suspensions of the formulations were administered via oral gavage at an AbA dose of 25 mg/kg. Plasma samples were collected and analyzed for drug content. SLH with a saturation level of 90% Seq enhanced the oral bioavailability of unformulated AbA by 31-fold, and super-SLH with saturation levels of 150, 200 and 250% Seq, enhanced the bioavailability by 11, 10 and 7-fold, respectively. In comparison with the commercial product Zytiga, SLH (90% Seq) increased the oral bioavailability 1.43-fold whereas super-SLH showed no improvement. A reasonable IVIVC existed between the performance of unformulated AbA, SLH and super-SLH, in the in vitro lipolysis and in vivo oral pharmacokinetic studies. SLH and super-SLH significantly enhanced the oral bioavailability of AbA. Additionally, supersaturation of SLH improved drug loading but did not correlate with enhanced AbA bioavailability.