目的 制备氯诺昔康(LN)醇质体凝胶剂, 并考察其体外经皮渗透特性。方法 采用乙醇注入法制备氯诺昔康醇质体, 以包封率为指标, 利用正交设计优化处方和制备工艺, 并对醇质体形态、粒径、Zeta电位及包封率进行评价, 并以卡波姆为基质制备醇质体凝胶;采用Franz扩散池和小鼠皮肤进行体外经皮渗透实验, 以HPLC测定药物浓度并计算药物累积渗透量、稳态透皮速率和皮内滞留量。结果 氯诺昔康醇质体外形圆整, 平均粒径为(385.6±59.2) nm, Zeta电位为(-23.49±2.38) mV, 平均包封率为(73.44±1.35)%。制得的醇质体凝胶剂为黄色半透明黏稠状胶体, 稳态透皮速率J为(2.81±0.68)μg·cm-2·h-1, 是其水混悬液的12.77倍, 是普通凝胶的3.51倍, 是体积分数30%乙醇水混悬液的2.60倍, 24 h时氯诺昔康在皮肤中的滞留量排序为醇质体凝胶>普通凝胶>体积分数30%乙醇水混悬液>水混悬液。结论 氯诺昔康醇质体凝胶制备工艺简便可行, 质量稳定可控, 可显著提高药物的透皮速率, 增加药物在皮肤中的滞留量。
Abstract
OBJECTIVE To prepare lornoxicam (LN) ethosomal gel and to study its transdermal permeation in vitro. METHODS The LN ethosomes were prepared by ethanol injection method. The formulation and the preparation method of ethosomes were optimized by orthogonal experiment using encapsulation efficiency as index. The morphology, particle size, Zeta potential and entrapment efficiency were evaluated, and the carbomer was added as the base for the preparation of the ethosomal gel. The penetration experiments of LN ethosomal gel through mouse skin were performed by Franz’s cell. The concentration of LN was determined by HPLC. The cumulative penetration amount, steady penetration rate and the skin deposition of the drug were calculated. RESULTSThe obtained ethosomes were spherical, the mean size and Zeta potential were (385.6±59.2) nm and (–23.49±2.38) mV, respectively. The mean entrapment efficiency of LN in ethosomes was (73.44±1.35)%. The LN ethosomal gel had a translucent yellow viscous colloidal appearance. The steady penetration rate of LN from ethosomal gel (2.81 μg·cm-2·h-1) was 12.77, 3.51 and 2.60 times higher than that from suspensions, gel and hydroethanolic suspensions of LN, respectively. The skin deposition of the drug at the end of the experiment was statistically greater from the ethosomal gel than from other control groups. CONCLUSION The gel is feasible in preparation technique, stable and controllable in quality and can improve transdermal penetration and increased the LN amount retain in the skin significantly.
关键词
氯诺昔康 /
醇质体凝胶 /
正交设计 /
经皮渗透
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Key words
lornoxicam /
ethosomal gel /
orthogonal design /
cutaneous permeation
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中图分类号：
R944
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参考文献
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脚注
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基金
烟台市科技发展计划项目(2010326)
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