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

Author(s) Schultz, H.B.; Wignall, A.D.; Thomas, N.; Prestidge, C.A.
Journal Int J Pharm
Date Published 2020 May 30

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 (S), 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% S enhanced the oral bioavailability of unformulated AbA by 31-fold, and super-SLH with saturation levels of 150, 200 and 250% S, enhanced the bioavailability by 11, 10 and 7-fold, respectively. In comparison with the commercial product Zytiga, SLH (90% S) 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.

DOI 10.1016/j.ijpharm.2020.119264
ISSN 1873-3476
Citation Int J Pharm. 2020;582:119264.

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