Nanonized progesterone formulation for improved oral bioavailability in healthy and pregnant rabbits

Abstract

The aim of this study is to evaluate and compare the oral bioavailability of nanonized progesterone (nano-PG) and micronized progesterone (micro-PG) sustained release tablet formulation in healthy and pregnant rabbits. High pressure compressed gas technology reduces the particle size from 1.72 ± 2.5 μm (micro-PG) to 800 ± 35 nm (nano-PG). DSC and XRD showed that both micro-PG and nano-PG were crystalline and exist as form I. Higher melting enthalpy of nano-PG indicated improved drug stability whereas XRD showed slight reduction in degree of crystallanity following nanonization. Nano-PG demonstrated 2-fold higher solubility in SDS aqueous solution and significantly higher permeability (p < 0.05) across porcine intestine compared to micro-PG. The pharmacokinetics of nano-PG and micro-PG was conducted in healthy and pregnant rabbits. The Cmax of nano-PG was higher in healthy and pregnant rabbits however the difference was significant in healthy rabbits only. The nano-PG demonstrated 30% and 18% higher bioavailability compared to micro-PG in healthy and pregnant rabbits, respectively. In conclusion, nanonization improves solubility, dissolution and bioavailability of PG in rabbits without affecting solid state characters.