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基于纳米结构脂质载体(NLC)的丙酸氯倍他索控释局部用凝胶:设计与体内表征

Nanostructured lipid carriers (NLC) based controlled release topical gel of clobetasol propionate: design and in vivo characterization.

作者信息

Nagaich Upendra, Gulati Neha

机构信息

Department of Pharmaceutics, Amity Institute of Pharmacy, Amity University, Noida, UP, India.

School of Pharmaceutical Sciences, IFTM University, Moradabad, UP, India.

出版信息

Drug Deliv Transl Res. 2016 Jun;6(3):289-98. doi: 10.1007/s13346-016-0291-1.

Abstract

Nanostructured lipid carrier (NLC)-based gel was developed as a potential topical system for clobetasol propionate (CP) topical delivery for the treatment of eczema. The characterizations of the prepared NLC formulation for topical application on the skin were assessed by means of morphology (SEM), particle size distribution, zeta potential analysis, drug entrapment efficiency, and in vitro drug release studies to select the optimized NLC formulation. The optimized NLC formulation encompasses particle size of 137.9 nm with -20.5 mV zeta potential and 0.224 polydispersity index which indicates good stability of NLC dispersion. NLC formulation showed a good entrapment efficiency of 78.5 % ± 0.03 with cumulative in vitro release 85.42 % up to 24 h. The optimized NLC formulation was suitably gelled and characterized for rheology, drug content, ex vivo drug permeation studies, and drug release kinetics studies. The permeation study revealed that the permeability parameters like steady-state flux (Jss), permeability coefficient (Kp), and enhancement ratio were significantly higher for NLC-based gel formulation as compared to marketed formulation of clobetasol propionate. The value of r (2) (Korsmeyer-Peppas equation) indicated good linearity showing anomalous (non-Fickian) diffusion viz. drug release is controlled by more than one process, i.e., superposition of both phenomenon, the diffusion controlled as well as swelling controlled release. The anti-inflammatory activity of NLC gel via paw oedema technique showed a rapid onset of action, as well as a prolonged duration of action as compared with the marketed gel.

摘要

纳米结构脂质载体(NLC)凝胶被开发为一种潜在的局部给药系统,用于丙酸氯倍他索(CP)的局部递送以治疗湿疹。通过形态学(扫描电子显微镜)、粒径分布、zeta电位分析、药物包封率和体外药物释放研究,对制备的用于皮肤局部应用的NLC制剂进行表征,以选择优化的NLC制剂。优化的NLC制剂粒径为137.9 nm,zeta电位为-20.5 mV,多分散指数为0.224,这表明NLC分散体具有良好的稳定性。NLC制剂显示出78.5%±0.03的良好包封率,24小时内的累积体外释放率为85.42%。对优化的NLC制剂进行适当凝胶化,并对其流变学、药物含量、离体药物渗透研究和药物释放动力学研究进行表征。渗透研究表明,与丙酸氯倍他索市售制剂相比,基于NLC的凝胶制剂的稳态通量(Jss)、渗透系数(Kp)和增强比等渗透参数显著更高。r(2)值(Korsmeyer-Peppas方程)表明具有良好线性,显示出异常(非Fickian)扩散即药物释放受不止一个过程控制,即扩散控制和溶胀控制释放这两种现象的叠加控制释放。通过爪肿胀技术对NLC凝胶进行抗炎活性研究,结果表明与市售凝胶相比,其起效迅速且作用持续时间延长。

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