工艺变更对祖师麻关节止痛膏体外释放及经皮渗透的影响

目的:考察祖师麻关节止痛膏生产工艺由溶剂法改成热压法后对产品体外动力学行为的影响。方法:采用溶剂法和热压法制备3批中试以上规模的样品,采用改良Franz扩散池法考察祖师麻关节止痛膏中指标成分(祖师麻甲素、水杨酸甲酯)的体外释放和经皮渗透情况。结果:溶剂法样品中祖师麻甲素、水杨酸甲酯的质量分别为73.72,494.67μg/贴;热压法样品中二者质量则分别为159.21,2 638.99μg/贴。溶剂法样品中祖师麻甲素、水杨酸甲酯的24 h平均累积释放量分别为2.04,12.21μg;热压法样品中二者的24 h平均累积释放量分别为2.16,36.24μg。溶剂法样品中祖师麻甲素、水杨酸甲酯的24 h平均累积透过量分别为0.38,2.79μg;热压法样品中二者的24 h平均累积透过量分别为0.40,7.49μg。热压法样品中祖师麻甲素的24 h累积释放量、累积透过量与溶剂法样品接近,无统计学差异;热压法样品中水杨酸甲酯的24 h累积释放量、累积透过量显著高于溶剂法样品(P<0.05)。结论:热压法对祖师麻关节止痛膏中祖师麻甲素、水杨酸甲酯的保留优于溶剂法,工艺变更对该制剂中祖师麻甲素体外动力学影响不显著,但由溶剂法改成热压法后,祖师麻关节止痛膏中水杨酸甲酯具有更高的累积释放量和累积透过量。

Effect of Process Change on in Vitro Release and Percutaneous Penetration of Zushima Guanjie Zhitong Gao

Objective:To investigate the effect of the production process of Zushima Guanjie Zhitong Gao from solvent method to hot-pressed method on in vitro kinetic behavior of this preparation. Method:Solvent and hot-pressed methods were used to prepare three batches of samples above pilot scale,and in vitro release and percutaneous penetration of the index components(7,8-dihydroxycoumarin and methyl salicylate)in Zushima Guanjie Zhitong Gao were investigated by modified Franz diffusing cells. Result:The contents of 7,8-dihydroxycoumarin and methyl salicylate in Zushima Guanjie Zhitong Gao prepared by solvent method were 73.72,494.67 μg/patch,and their contents in hot-pressed method samples were 159.21,2 638.99 μg/patch,respectively. In the solvent method samples,the average cumulative release amounts of 7,8-dihydroxycoumarin and methyl salicylate in 24 h were 2.04,12.21 μg,and their average cumulative release amounts in 24 h of hotpressed method samples were 2.16, 36.24 μg, respectively. In the solvent method samples, the average cumulative permeation amounts of 7,8-dihydroxycoumarin and methyl salicylate in 24 h were 0.38,2.79 μg,and they were 0.40,7.49 μg in hot-pressed method samples. The cumulative release and permeation amounts in24 h of 7,8-dihydroxycoumarin in the hot-pressed method samples were basically the same as those of the solvent method samples,but the cumulative release and permeation amounts in 24 h of methyl salicylate in the hot-pressed method samples were significantly higher than those of the solvent method samples(P<0.05).Conclusion: The retention of 7,8-dihydroxycoumarin and methyl salicylate by hot-pressed method is better than that of the solvent method. The process change has no significant effect on the in vitro kinetics of 7,8-dihydroxycoumarin in Zushima Guanjie Zhitong Gao,however,after the change from the solvent method to the hot-pressed method,the methyl salicylate in this preparation has a higher cumulative release and permeation amounts.