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通过开发和优化速溶膜提高瑞舒伐他汀钙的药代动力学和药效学

Enhancing Pharmacokinetics and Pharmacodynamics of Rosuvastatin Calcium through the Development and Optimization of Fast-Dissolving Films.

作者信息

Ashraf Ibrahim, Hanna Pierre A, Gad Shadeed, Abd-Allah Fathy I, El-Say Khalid M

机构信息

Department of Pharmaceutics, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt.

Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Al-Azhar University, Cairo 11651, Egypt.

出版信息

Pharmaceutics. 2023 Nov 19;15(11):2640. doi: 10.3390/pharmaceutics15112640.

Abstract

Rosuvastatin (RSV) is a widely used cholesterol-lowering medication, but its limited bioavailability due to its susceptibility to stomach pH and extensive first-pass metabolism poses a significant challenge. A fast-dissolving film (FDF) formulation of RSV was developed, characterized, and compared to the conventional marketed tablet to address this issue. The formulation process involved optimizing the thickness, disintegration time, and folding durability. All formulations were assessed for in vitro disintegration, thickness, folding endurance, in vitro dissolution, weight, and content uniformity. The study's results revealed that the optimized RSV-FDF displayed a significantly faster time to maximum plasma concentration (t) of 2 h, compared to 4 h for the marketed tablet. The maximum plasma concentration (C) for the RSV-FDF (1.540 µg/mL ± 0.044) was notably higher than that of the marketed tablet (0.940 µg/mL ± 0.017). Additionally, the pharmacodynamic assessment in male Wistar rats demonstrated that the optimized RSV-FDF exhibited an improved lipid profile, including reduced levels of low-density lipoproteins (LDLs), elevated high-density lipoproteins (HDLs), decreased triglycerides (TGs), and lower very-low-density lipoproteins (VLDLs) compared to the conventional tablet. These findings underscore the potential of RSV-FDFs as a promising alternative to enhance the bioavailability and therapeutic efficacy of rosuvastatin in treating dyslipidemia. The faster onset of action and improved lipid-lowering effects make RSV-FDFs an attractive option for patients requiring efficient cholesterol management.

摘要

瑞舒伐他汀(RSV)是一种广泛使用的降胆固醇药物,但其易受胃内酸碱度影响且首过代谢广泛,导致生物利用度有限,这构成了重大挑战。为解决这一问题,研发了瑞舒伐他汀的速溶膜(FDF)制剂,对其进行了表征,并与传统市售片剂进行了比较。制剂过程包括优化厚度、崩解时间和折叠耐久性。对所有制剂进行了体外崩解、厚度、耐折性、体外溶出度、重量和含量均匀度评估。研究结果显示,优化后的瑞舒伐他汀-FDF达到最大血药浓度(t)的时间显著更快,为2小时,而市售片剂为4小时。瑞舒伐他汀-FDF的最大血药浓度(C)(1.540μg/mL±0.044)明显高于市售片剂(0.940μg/mL±0.017)。此外,在雄性Wistar大鼠中的药效学评估表明,与传统片剂相比,优化后的瑞舒伐他汀-FDF显示出改善的血脂谱,包括低密度脂蛋白(LDL)水平降低、高密度脂蛋白(HDL)升高、甘油三酯(TG)降低以及极低密度脂蛋白(VLDL)降低。这些发现强调了瑞舒伐他汀-FDF作为一种有前景的替代方案,可提高瑞舒伐他汀治疗血脂异常的生物利用度和治疗效果。更快的起效时间和改善的降脂效果使瑞舒伐他汀-FDF成为需要有效管理胆固醇的患者的有吸引力选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2498/10675329/f624c76e3208/pharmaceutics-15-02640-g001.jpg

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