温经止痛凝胶膏剂体外释放度及透皮特性的研究

Study on release and permeation behavior of Wenjingzhitong Gel Paste in vitro

目的 研究温经止痛凝胶膏剂的体外释放及透皮特性以及挥发油包合技术对挥发油透皮特性的影响,为开发温经止痛处方贴敷预防和治疗痛经的药物新型给药系统提供实验支持。方法分别以透析膜和大鼠皮肤为屏障,以扩散池法进行体外释放和透皮实验,以方中君臣药当归、川芎的主要有效成分之一的藁本内酯为指标,利用高效液相色谱法分析,测定温经止痛凝胶膏剂释放介质和透皮接收液中的药物浓度,分别以累积释放量和透皮量对时间进行回归计算,计算12 h的累计释放率和24 h的透皮速率。结果藁本内酯自温经止痛凝胶膏剂中体外释放的方程为Q=4.37t+1.79,r=0.993,释放速率为4.37μg/(cm2·h),12 h累计释放率为90.9%;24 h温经止痛凝胶膏剂挥发油包合组的透皮特性方程为:Q=1.45t+6.06,透皮速率为1.45μg/(cm2·h);挥发油包合组24 h的透皮特性方程为Q=2.65t+11.99,透皮速率为2.65μg/(cm2·h)。结论藁本内酯的释放速率远大于透皮速率,释放速率可保证其稳定透皮的动力,其透皮过程不受其释放的限制;包合技术可使藁本内酯的透皮速率降低,但是影响不大,挥发油可包合后再加入凝胶膏剂中。

Objective To study the release and permeation behavior of Wenjingzhitong Gel Paste in vitro to be used in the treatment of dysmenorrehea prevention and care and to study the influence of inclusion technique to the permeation behavior of essential oil. Methods Dialysis membrane and rat skin were used as the barriers respectively. The release and permeation experiment were carried out with Franz diffusion cell in vitro. Ligustilide, the main active ingredient of the monarch drug(Angelica sinensis) and ministerial drug(Ligusticum wallichii) in the prescription, was used as a marker, and measured by high performance liquid chromatography(HPLC) method. The accumulated and permeation amount were regressed linearly to time to calculate the release and permeation rate separately. Results The release equation of ligustilide from Wenjingzhitong Gel Paste was Q=4.37t+1.79, r=0.993; the release rate was 4.37 μg/(cm2·h)and the accumulated release ratio in 12 h was 90.9%. Permeation equation of Wenjingzhitong Gel Paste with inclusion technique applied to essential oil in 24 h was Q=1.45t+6.06 and the release rate was 1.45 μg/(cm2·h), while permeation equation without inclusion technique was Q=2.65t+11.99 and the release rate was 2.65 μg/(cm2·h). Conclusion The release rate of ligustilide from Wenjingzhitong Gel Paste is much greater than the permeation one, which can make ligustilide permeate sustainedly. Inclusion technique makes the permeation rate decrease little, thus the essential oil can be included in the cyclodectrin first and then be added into the hydrogel patch.