Self-microemulsifying sustained-release pellet of Ginkgo biloba extract: Preparation, in vitro drug release and pharmacokinetics study in beagle dogs

Abstract

Ginkgo biloba extract (GBE50), the fifth generation extract of Ginkgo biloba, has been widely used in clinical treatment. This study was aimed at developing self-microemulsifying drug delivery system sustained-release pellets (SMEDDS-SR pellets) to achieve sustained release and increased the oral bioavailability of GBE50. Solubility studies and Pseudo-ternary phase diagrams were investigated to optimize the suitable compositions of SMEDDS-SR pellets. The optimal formulation of GBE50-SMEDDS consisting of oil (16.7% MCT), surfactant (33.4% Cremophor EL35), cosurfactant (33.4% PEG 400) and drug (16.7% GBE50) was obtained. The GBE50-SMEDDS-SR pellets were prepared by mixing GBE50-SMEDDS with diluent agent (MCC), disintegration agent (PVPP) and coating material of ethyl cellulose (EC) using extrusion spheronization method. The Morphology study of GBE50-SMEDDS-SR pellets after dispersion in water revealed a spherical and homogeneous structure of droplets (51.6 ± 1.8) nm. The in vitro release data revealed the sustained-release effect of GBE50-SMEDDS-SR pellets. Pharmacokinetics study in beagle dogs after oral administration yielded relative bioavailability (Fr) of 160.24% and 236.18% for GBE50-SMEDDS and GBE50-SMEDDS-SR pellets, respectively. Collectively, these results indicated that the SMEDDS-SR pellets could be an effective delivery system to achieve sustained release and improved oral bioavailability of GBE50.