Preparation and in vivo evaluation of self- microemulsifyingdrug delivery system for oral delivery of GC-8

• Main Authors: Huai-En Lu, 呂懷恩
• Other Authors: 許明照
• Format: Others
• Language: zh-TW
• Published: 2010
• Online Access: http://ndltd.ncl.edu.tw/handle/09483030277458516687

碩士 === 臺北醫學大學 === 藥學研究所 === 98 === Oral absorption of hydrophobic drugs can be significantly improved using lipid-based drug delivery systems. Microemulsions are clear, stable, isotropic mixtures of oil, water and surfactant, frequently in combination with a cosurfactant. They have been shown to be able to protect labile drug, increase drug solubility and increase bioavailability. Self- microemulsifying drug delivery system (SMEDDS) is a pre-microemulsifying system consisting of oil, surfactant, co-surfactant and drug substance, which can form a w/o microemulsion under conditions of gastrointestinal fluid and gastrointestinal motility after oral administration. In this study, the model drug, GC-8, is a mixture extracted from the gamboge resin of Garcinia hanburyi Hook. f. in southeast Asia. Gambogic acid (GA) is one of those components，and has been reported previously to have potent cytotoxicities against various cancer cell lines and to be a potent apoptosis inducer. However, GC-8 is a poorly water-soluble drug and the oral bioavailability is very low. The main purpose of this study was to develop SMEDDS for oral bioavailability enhancement of GC-8. The solubility of GC-8 was determined in various vehicles. Ternary phase diagrams were used to evaluate the self-microemulsfication domain. The in vivo studies were used to evaluate the pharmacokinetics. The optimized formulation (GC-8-SMEDDS-C) was composed of Capryol PGMC(35%), TPGS(30%), and Trancutol(25%). The solubility of GC-8 significantly increased in SMEDDS from 2.18±0.39 μg/mL to 41.96±1.92 mg/mL, rapid self-microemulsification in aqueous media, and forming droplet size in the range of microemulsion. In Pharmacokinetic study, GC-8-SMEDDS could significantly increase the oral absorption of GC-8 compare with GC-8 suspension. It seems that the GC-8-SMEDDS formulation can be used to improve its oral bioavailability.