Kassem Abdulsalam M, Ibrahim Hany M, Samy Ahmed M
a Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy , Al-Azhar University , Cairo , Egypt.
J Microencapsul. 2017 May;34(3):319-333. doi: 10.1080/02652048.2017.1328464. Epub 2017 May 23.
The objective of this study was to develop and optimise self-nanoemulsifying drug delivery system (SNEDDS) of atorvastatin calcium (ATC) for improving dissolution rate and eventually oral bioavailability. Ternary phase diagrams were constructed on basis of solubility and emulsification studies. The composition of ATC-SNEDDS was optimised using the Box-Behnken optimisation design. Optimised ATC-SNEDDS was characterised for various physicochemical properties. Pharmacokinetic, pharmacodynamic and histological findings were performed in rats. Optimised ATC-SNEDDS resulted in droplets size of 5.66 nm, zeta potential of -19.52 mV, t of 5.43 min and completely released ATC within 30 min irrespective of pH of the medium. Area under the curve of optimised ATC-SNEDDS in rats was 2.34-folds higher than ATC suspension. Pharmacodynamic studies revealed significant reduction in serum lipids of rats with fatty liver. Photomicrographs showed improvement in hepatocytes structure. In this study, we confirmed that ATC-SNEDDS would be a promising approach for improving oral bioavailability of ATC.
本研究的目的是开发并优化阿托伐他汀钙（ATC）的自纳米乳化药物递送系统（SNEDDS），以提高溶出速率并最终提高口服生物利用度。基于溶解度和乳化研究构建了三元相图。使用Box-Behnken优化设计对ATC-SNEDDS的组成进行了优化。对优化后的ATC-SNEDDS的各种理化性质进行了表征。在大鼠中进行了药代动力学、药效学和组织学研究。优化后的ATC-SNEDDS液滴尺寸为5.66 nm，ζ电位为-19.52 mV，t为5.43分钟，且无论介质pH如何，均可在30分钟内完全释放ATC。优化后的ATC-SNEDDS在大鼠体内的曲线下面积比ATC混悬液高2.34倍。药效学研究表明，患有脂肪肝的大鼠血清脂质显著降低。显微照片显示肝细胞结构有所改善。在本研究中，我们证实ATC-SNEDDS将是提高ATC口服生物利用度的一种有前景的方法。
