Influence of polyvinylpyrrolidone quantity on the solubility, crystallinity and oral bioavailability of fenofibrate in solvent-evaporated microspheres

Abstract

The objective of this study is to explore the influence of polyvinylpyrrolidone (PVP) quantity on the solubility, crystallinity and oral bioavailability of poorly water-soluble fenofibrate in solvent-evaporated microspheres. Numerous microspheres were prepared with fenofibrate, sodium lauryl sulphate (SLS) and PVP using the spray-drying technique. Their aqueous solubility, dissolution, physicochemical properties and pharmacokinetics in rats were assessed. The drug in the solvent-evaporated microspheres composed of fenofibrate, PVP and SLS at the weight ratio of 1:0.5:0.25 was not entirely changed to the amorphous form and partially in the microcrystalline state. However, the microspheres at the weight ratio of 1:4:0.25 provided the entire conversion to the amorphous form. The latter microspheres, with an improvement of about 115 000-fold in aqueous solubility and 5.6-fold improvement in oral bioavailability compared with the drug powder, gave higher aqueous solubility and oral bioavailability compared with the former. Thus, PVP quantity played an important role in these properties of fenofibrate in the solvent-evaporated microspheres.

Keywords:

• Fenofibrate
• solvent-evaporated microsphere
• polyvinylpyrrolidone
• aqueous solubility
• crystallinity
• oral bioavailability

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper. This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (MEST) (No. 2015R1A2A2A05027872).