Improved systemic delivery of insulin by condensed drug loading in a dimpled suppository
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- Matsumoto Akihiro
- Laboratory of Pharmaceutics, Faculty of Pharmacy, Osaka Ohtani University Hanshin Pharmacy, Co. Ltd.
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- Murakami Kayoko
- Laboratory of Pharmaceutics, Faculty of Pharmacy, Osaka Ohtani University
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- Watanabe Chie
- Laboratory of Pharmaceutics, Faculty of Pharmacy, Osaka Ohtani University
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- Murakami Masahiro
- Laboratory of Pharmaceutics, Faculty of Pharmacy, Osaka Ohtani University
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<p>The development of peptide therapeutics owing to the advances in biotechnology has overcome some unmet medical needs; however, the route of administration is still limited to injections. Systemic delivery of insulin via an enteral route remains a great challenge due to its instability and low mucosal permeability. In this study, we investigated the effect of drug condensation in a suppository on the efficacy of insulin after rectal administration. Suppositories with dimples are prepared by a mold method using a hard fat (Suppocire® AM). Insulin or fluorescein isothiocyanate-dextran (molecular weight: 3,000-5,000) (FD4) as a model of a hydrophilic macromolecule was loaded in the dimples, and sealed with other lipids with different melting points. The in vitro release test showed that the time to 50% drug release depends on the melting point of the lipid for sealing but not on the number of dimples. The suppositories with one-, or three-dimple containing insulin and caprylocaproyl macrogol-8 glyceride (Labrasol®) were administered to rats at 0.5 U/head. The reduction in plasma glucose level was more significant for the one-dimple-type suppository than for the three-dimple-type although the one-dimple-type suppository contained less amount of Labrasol by one-third compared to the three-dimple-type. These results suggest that condensation of an insulin dose in a limited surface area of a suppository improves systemic availability via the rectal route with a reduced amount of an absorption enhancer.</p>
収録刊行物
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- Drug Discoveries & Therapeutics
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Drug Discoveries & Therapeutics 11 (6), 293-299, 2017
特定非営利活動法人 バイオ＆ソーシャル・サイエンス推進国際研究交流会