Predicting effect of solubilizers on the oral absorption of a low soluble drug by considering the regional differences in membrane permeability and solubility

2014 Fiscal Year Final Research Report

• Project/Area Number: 25860133
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Medical pharmacy
• Research Institution: Hiroshima International University
• Principal Investigator: TANAKA Yusuke 広島国際大学, 薬学部, 助教 (10435068)
• Co-Investigator(Kenkyū-buntansha): NAGATA Shunji 広島国際大学, 薬学部, 教授 (00412354)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: 消化管吸収 / 吸収部位差 / 吸収予測

Outline of Final Research Achievements

This study aimed to develop a novel approach for predicting the oral absorption of low-solubility drugs and the effect of solubilizers by considering regional differences in solubility and permeability within the gastrointestinal(GI) tract using newly developed simulated upper and lower intestinal fluids.
The solubility and permeability of AZ estimated using the upper and lower simulated GI fluids were about 15.8 and 34.3 g/mL and 3.9 and 3.3 ×10-5　cm/sec, respectively. When adding dimethyl sulfoxide and beta-cyclodextrin as solubilizers into the two simulated GI fluids, the solubility and permeability were almost unchanged in the both fluids. On the other hand, the AZ solubility was significantly increased by adding Vitamin E-TPGS while the permeability was to some extent decreased. The predicted Fa values using these solubility and permeability data were correspond closely to the in vivo data, and its absorption enhancement by solubilizers was also predicted accurately.

Free Research Field

生物薬剤学