Department of Pharmacy, Fuzong Clinical Medical College of Fujian Medical University (900 Hospital of the Joint Logistics Team), 156 West Second-Ring Road, Fuzhou, 350025, PR China.
AAPS J. 2024 Nov 22;27(1):6. doi: 10.1208/s12248-024-00992-w.
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.
他克莫司（FK506）作为一种免疫抑制剂的应用受到其低水溶性和生物利用度的限制。在我们之前的研究中，自微乳药物传递系统（SMEDDS）成功地提高了 FK506 的溶解度。本研究专注于液体 SMEDDS 的固化，以结合液体 SMEDDS 和固体剂型的优点。在所评估的几种多孔硅吸附剂中，Aeroperl® 300 Pharma 在粒径、体外溶出度、吸附剂-药物相容性和可压性方面表现出最佳性能。并且预先用聚乙烯吡咯烷酮 K30 对吸附剂进行包衣处理，可实现完全药物释放。基于羟丙甲基纤维素的基质片剂被开发出来，以实现 FK506 的缓释。差示扫描量热法和 X 射线粉末衍射表明，固化的 SMEDDS 和片剂中的 FK506 以分子或无定形状态存在。体内药代动力学研究表明，与市售产品 Advagraf®相比，自制片剂具有更高的生物利用度（179.02%）。本研究为 FK506 提供了一种具有改善的溶解和生物利用度的有前途的候选药物，以及 SMEDDS 开发的有前景的平台。
