Development of Solidified Self-microemulsifying Delivery Systems Containing Tacrolimus for Enhanced Dissolution and Pharmacokinetic Profile.

IF 5 3区医学 Q1 PHARMACOLOGY & PHARMACY

AAPS Journal Pub Date : 2024-11-22 DOI:10.1208/s12248-024-00992-w

Lingjun Zeng, Youye Wang, Zhihong Liu, Xiaomu Hu, Changqing Zheng, Lingyan Yao, Minxin Zhang, Xianquan Feng, Hongtao Song

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引用次数: 0

Abstract

The use of tacrolimus (FK506) as an immunosuppressant is limited by its low aqueous solubility and bioavailability. The self-microemulsifying drug delivery system (SMEDDS) has successfully improved the solubility of FK506 in our previous study. This study focused on the solidification of liquid SMEDDS to capture the benefits of both liquid SMEDDS and solid dosage forms. Among several porous silica adsorbents evaluated, Aeroperl® 300 Pharma showed the best performance in terms of droplet size, in vitro dissolution, adsorbent-drug compatibility, and tabletabilities. And precoating the adsorbent with polyvinylpyrrolidone K30 resulted in complete drug release. Hydroxypropyl methylcellulose based matrix tablet was developed to achieve a sustained release of FK506. Differential scanning calorimetry and X-ray powder diffraction indicated that FK506 was present in a molecular or amorphous state in the solidified SMEDDS and tablets. In vivo pharmacokinetic studies showed that the self-prepared tablet had improved bioavailability (179.02%) compared to the marketed product Advagraf®. This study provided a promising candidate with improved dissolution and bioavailability for FK506 and a prospective platform for SMEDDS development.

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开发含有他克莫司的固化自微乳化给药系统，以提高溶解度和药代动力学特征。

他克莫司（FK506）的水溶性和生物利用度较低，限制了其作为免疫抑制剂的使用。在我们之前的研究中，自微乳化给药系统（SMEDDS）已成功改善了 FK506 的溶解度。本研究的重点是液态 SMEDDS 的固化，以获得液态 SMEDDS 和固态剂型的优点。在评估的几种多孔二氧化硅吸附剂中，Aeroperl® 300 Pharma 在液滴大小、体外溶解度、吸附剂与药物的相容性和片剂性能方面表现最佳。而用聚乙烯吡咯烷酮 K30 对吸附剂进行预涂则可使药物完全释放。为了实现 FK506 的持续释放，我们开发了基于羟丙基甲基纤维素的基质片剂。差示扫描量热法和 X 射线粉末衍射表明，FK506 以分子或无定形状态存在于固化的 SMEDDS 和片剂中。体内药代动力学研究表明，与市售产品 Advagraf® 相比，自制剂片剂的生物利用率更高（179.02%）。这项研究为 FK506 提供了一种溶解度和生物利用度均得到改善的候选药物，并为 SMEDDS 的开发提供了一个前景广阔的平台。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

AAPS Journal 医学-药学

CiteScore

7.80

自引率

4.40%

发文量

109

审稿时长

1 months

期刊介绍： The AAPS Journal, an official journal of the American Association of Pharmaceutical Scientists (AAPS), publishes novel and significant findings in the various areas of pharmaceutical sciences impacting human and veterinary therapeutics, including: · Drug Design and Discovery · Pharmaceutical Biotechnology · Biopharmaceutics, Formulation, and Drug Delivery · Metabolism and Transport · Pharmacokinetics, Pharmacodynamics, and Pharmacometrics · Translational Research · Clinical Evaluations and Therapeutic Outcomes · Regulatory Science We invite submissions under the following article types: · Original Research Articles · Reviews and Mini-reviews · White Papers, Commentaries, and Editorials · Meeting Reports · Brief/Technical Reports and Rapid Communications · Regulatory Notes · Tutorials · Protocols in the Pharmaceutical Sciences In addition, The AAPS Journal publishes themes, organized by guest editors, which are focused on particular areas of current interest to our field.