尼莫地平水凝胶贴剂的制备及其体外透皮性能研究

目的:制备尼莫地平水凝胶贴剂,并考察不同因素对尼莫地平体外透皮性的影响。方法:以羧甲基纤维素钠为骨架材料制备尼莫地平水凝胶贴剂,采用透皮扩散试验仪,以离体小鼠皮肤为屏障进行体外透皮实验,高效液相色谱法测定药物浓度,并计算药物累积透皮量Q和透皮速率常数Js。以Q值和Js值为指标,筛选投药量、透皮促进剂的种类(薄荷醇、氮酮、油酸)和用量。结果:最佳投药量为4 mg·cm-2,不同透皮促进剂对尼莫地平均有透皮促进作用,其中以5%油酸作用最显著。以5%油酸为透皮促进剂制备的样品的透皮吸收行为符合零级动力学过程,Js值为28.10μg·cm-2·h-1,12 h单位面积Q值为342.58μg·cm-2。结论:尼莫地平水凝胶贴剂可以开发为经皮给药制剂。

Preparation of Nimodipine Hydrogel Patch and Its in Vitro Percutaneous Permeability

OBJECTIVE： To prepare Nimodipine hydrogel patch and to investigate the effects of different factors on the in vitro percutaneous permeability of nimodipine.METHODS： Nimodipine hydrogel patch was prepared with sodium carboxymethylcellulose as matrix.The permeation flux of nimodipine through excised mice skin in vitro was determined using Franz diffusion cell.The content of nimodipine was measured by HPLC.Accumulative transdermal delivery of nimodipine（Q） and transdermal speed constant（Js） were calculated.The loading amounts,type of transdermal enhancer（menthol,azone and oleic acid） and their content were optimized with the value of Q and Js as index.RESULTS： The best loading amount was 4 mg·cm^-2.Different transdermal enhancers were found to increase the percutaneous permeability of nimodipine.5% oleic acid had the best penetration enhancing effect.The permeation of samples containing 5% oleic acid was in accordance with the zero-order kinetics.Nimodipine hydrogel transdermal patch presented high Js of 28.10 μg·cm^-2·h^-1 and Q of 342.58 μg·cm^-2 in 12 h.CONCLUSION： Nimodipine hydrogel patch has good potential for transdermal delivery.