Development of new in vitro digestion to predict oral absorption of drugs from lipid based formulations

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K06658
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47060:Clinical pharmacy-related
• Research Institution: Setsunan University (2023); Hiroshima International University (2021-2022)
• Principal Investigator: Tanaka Yusuke 摂南大学, 薬学部, 講師 (10435068)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 消化管吸収 / 脂質製剤 / 過飽和溶解 / 経口剤 / 吸収予測

Outline of Final Research Achievements

The aim of this study is to establish and test an in vitro digestion-in situ absorption model that mimic in vivo drug flux by employing physiologically relevant value of membrane surface area (S)/volume (V) ratio for accurate prediction of performance of lipid-based formulations. A simultaneous in vitro digestion-permeation experiment was also performed using a side-by-side diffusion cell with a dialysis membrane having a low S/V value for comparison purpose. Cinnarizine (CNZ) was selected as a model for poorly water-soluble drug.
In vitro drug fluxes across dialysis membrane differed depending on formulations investigated. The obtained in vitro data did not correlate with in vivo oral AUCs. On the other hand, new model successfully predicted in vivo oral absorption of CNZ. This study demonstrated the importance of mimicking the in vivo drug absorption rate in the predictive model.

Free Research Field

薬剤学

Academic Significance and Societal Importance of the Research Achievements

脂質分散製剤(LBF)は薬物の溶解性を改善する手法として極めて有用である。一方、LBFはその有用性が実証されているにもかかわらず、その市販医薬品に占める割合はごくわずかである。これは、LBFからの薬物吸収機構が十分に解明されておらず、消化管吸収性改善効果の予測が困難なため、可溶化技術としてLBFを選択しにくいことが原因である。本課題では実際の薬物吸収速度を再現したLBFからの薬物吸収性評価法を構築した。本研究により、LBF処方の最適化が容易となり、難水溶性化合物の経口剤開発に貢献できる。