Lipid-based formulations for improving oral absorption of poorly water-soluble drugs

• Project/Area Number: 16K18967
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Medical pharmacy
• Research Institution: Setsunan University
• Principal Investigator: Higashino Haruki 摂南大学, 薬学部, 助教 (60736784)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2016: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
• Keywords: 自己乳化型製剤 / 難水溶性薬物 / 過飽和溶解 / 脂質分散製剤 / 難溶性薬物 / 消化管吸収

Outline of Final Research Achievements

As one of the formulation techniques to improve oral absorption of poorly water-soluble drugs, lipid-based formulation (LBF) attracts much attention from the pharmaceutical companies. In this study, the performance of LBFs in the gastrointestinal (GI) tract, such as the release of loaded drugs along with the dilution by the GI fluid and the digestion of lipid components by lipase was investigated in vitro and in vivo.
As the results, medium-chain (MC) lipids were rapidly digested by lipase and released drugs induced the supersaturation. This step contributed to the increase in the absorption rate and the systemic exposure of drugs in vivo. Therefore, in order to design the potent LBFs for poorly water-soluble drugs, release profiles of drugs from LBFs should be observed carefully under various conditions.

Academic Significance and Societal Importance of the Research Achievements

近年の医薬品開発では、難水溶性を示す候補化合物の数が増えている。一方、これら化合物を実際の経口製剤として開発する場合、投与後、消化管内で速やかに溶解し体内に吸収される必要がある。本研究では、難水溶性薬物の溶解性を改善させる手法の一つである自己乳化型製剤を調製し、経口投与後の消化管内での薬物の放出性や血中曝露量の改善効果に関する検討を行い、吸収メカニズムの一つとして過飽和溶解の関与を明らかにした。

Research Products

• [Presentation] 難溶解性薬物の経口投与後の血中曝露の改善：自己乳化型製剤の有用性の検証 (2018)
  • Author(s): 江上 優香、東野 晴輝、南 景子、片岡 誠、山下伸二
  • Organizer: 日本薬剤学会第33年会
• [Presentation] 難溶解性薬物の経口投与後の血中曝露の改善：自己乳化型製剤の有用性の検証 (2018)
  • Author(s): 木村 直孝、東野 晴輝、南 景子、片岡 誠、山下伸二
  • Organizer: 創剤フォーラム第24回若手研究会
• [Presentation] Enhancing the systemic exposure of poorly-soluble drugs after oral administration to rats using self-microemulsifying system (SMEDDS) (2018)
  • Author(s): Haruki Higashino, Keiko Minami, Makoto Kataoka, Shinji Yamashita
  • Organizer: The 2nd Workshop for Korea-Japan Young Scientists on Pharmaceutics
  • Int'l Joint Research
• [Presentation] 脂質分散製剤による難水溶性薬物の経口デリバリー：組成比と薬物吸収率の関係 (2017)
  • Author(s): 浦郷真南、東野晴輝、南景子、片岡誠、山下伸二
  • Organizer: 第33回日本DDS学会学術集会
• [Presentation] 難溶性薬物の経口吸収改善を目的とした脂質分散製剤（Lipid-based formulation）の設計：過飽和溶解を考慮した製剤化 (2016)
  • Author(s): 東野晴輝、野村勇太、浦郷真南、南景子、片岡誠、山下伸二
  • Organizer: 第32回日本DDS学会学術集会
  • Place of Presentation: グランシップ（静岡県コンベンションアーツセンター
  • Year and Date: 2016-06-30
• [Presentation] 脂質分散製剤 （Lipid-based formulation）からの薬物吸収機構の解析：消化管内での過飽和溶解の寄与 (2016)
  • Author(s): 野村勇太、東野晴輝、浦郷真南、南景子、片岡誠、山下伸二
  • Organizer: 日本薬剤学会第31年会
  • Place of Presentation: 大宮ソニックシティ
  • Year and Date: 2016-05-19