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应用响应面法优化局部制剂中尼美舒利的渗透。

Applying response surface methodology to optimize nimesulide permeation from topical formulation.

机构信息

Division of Pharmacy and Pharmaceutical Science, School of Applied Sciences, University of Huddersfield, Huddersfield, HD1 3DH, UK.

出版信息

Pharm Dev Technol. 2013 Nov-Dec;18(6):1391-8. doi: 10.3109/10837450.2012.723721. Epub 2012 Sep 20.

Abstract

Nimesulide is a non-steroidal anti-inflammatory drug that acts through selective inhibition of COX-2 enzyme. Poor bioavailability of this drug may leads to local toxicity at the site of aggregation and hinders reaching desired therapeutic effects. This study aimed at formulating and optimizing topically applied lotions of nimesulide using an experimental design approach, namely response surface methodology. The formulated lotions were evaluated for pH, viscosity, spreadability, homogeneity and in vitro permeation studies through rabbit skin using Franz diffusion cells. Data were fitted to linear, quadratic and cubic models and best fit model was selected to investigate the influence of permeation enhancers, namely propylene glycol and polyethylene glycol on percutaneous absorption of nimesulide from lotion formulations. The best fit quadratic model explained that the enhancer combination at equal levels significantly increased the flux and permeability coefficient. The model was validated by comparing the permeation profile of optimized formulations' predicted and experimental response values, thus, endorsing the prognostic ability of response surface methodology.

摘要

尼美舒利是一种非甾体抗炎药,通过选择性抑制 COX-2 酶起作用。这种药物的生物利用度差可能导致聚集部位的局部毒性,并阻碍达到所需的治疗效果。本研究旨在通过实验设计方法(即响应面法)来配制和优化尼美舒利的局部用乳液。通过 Franz 扩散池评估了所配制的乳液的 pH 值、粘度、铺展性、均匀性和体外渗透研究。数据拟合为线性、二次和三次模型,并选择最佳拟合模型来研究渗透促进剂丙二醇和聚乙二醇对尼美舒利从乳液制剂经皮吸收的影响。最佳拟合二次模型表明,在同等水平下的增强剂组合显著增加了通量和渗透系数。通过比较优化配方的预测和实验响应值的渗透曲线来验证模型,从而证明响应面法的预测能力。

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