Self nanoemulsifying drug delivery system (SNEDDS) of Rosuvastatin calcium: Design, formulation, bioavailability and pharmacokinetic evaluation
Self nanoemulsifying drug delivery system (SNEDDS) of Rosuvastatin calcium: Design, formulation, bioavailability and pharmacokinetic evaluation
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DOI：
10.1016/j.colsurfb.2013.08.025
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发表时间：
2013-12-01
影响因子：
5.8
通讯作者：
Abdu, Siyad
中科院分区：
文献类型：
--
作者：
Balakumar, Krishnamoorthy;Raghavan, Chellan Vijaya;Abdu, Siyad
本研究的目的是利用自纳米乳化给药系统（SNEDDS）提高瑞舒伐他汀钙的溶解度和生物利用度。采用合适的表面活性剂和助表面活性剂对包括精油在内的各种油脂的自乳化性能进行了评价。基于瑞舒伐他汀钙溶解度分析构建了三元相图，以优化体系。评价制备的制剂的自乳化时间、稀释稳健性、液滴尺寸测定和ζ电位分析。发现该系统在不同pH介质和稀释体积下具有耐用性。优化体系的小球尺寸小于200 nm，这可能是可接受的纳米乳液尺寸范围。所选CN 7 SNEDDS制剂（肉桂油30%; Labrasol 60%; Capmul MCM C8 10%）的ζ电位为-29.5 +/-0.63，平均粒度分布为122 nm。体外药物释放研究表明，与市售制剂相比，CN 7 SNEDDS的溶出度显著增加。在生物利用度和药代动力学评价中使用内部开发的测定大鼠血浆中瑞舒伐他汀钙的HPLC方法。自纳米乳化制剂的相对生物利用度比混悬制剂高2.45倍。使用PKSolver 2.0处理获得的血药浓度数据，最佳拟合为一室模型。(C)2013爱思唯尔有限公司版权所有。
The aim of the present study is to improve solubility and bioavailability of Rosuvastatin calcium using self nanoemulsifying drug delivery system (SNEDDS). Self emulsifying property of various oils including essential oils was evaluated with suitable surfactants and co-surfactants. Ternary phase diagrams were constructed based on Rosuvastatin calcium solubility analysis for optimizing the system. The prepared formulations were evaluated for self emulsifying time, robustness to dilution, droplet size determination and zeta potential analysis. The system was found to be robust in different pH media and dilution volume. The globule size of the optimized system was less than 200 nm which could be an acceptable nanoemulsion size range. The zeta potential of the selected CN 7 SNEDDS formulation (cinnamon oil 30%; labrasol 60%; Capmul MCM C8 10%) was -29.5 +/- 0.63 with an average particle size distribution of 122 nm. In vitro drug release studies showed remarkable increase in dissolution of CN7 SNEDDS compared to marketed formulation. In house developed HPLC method for determination of Rosuvastatin calcium in rat plasma was used in the bioavailability and pharmacokinetic evaluation. The relative bioavailability of self nanoemulsified formulation showed an enhanced bioavailability of 2.45 times greater than that of drug in suspension. The obtained plasma drug concentration data was processed with PKSolver 2.0 and it was best fit into the one compartment model. (C) 2013 Elsevier B.V. All rights reserved.