溶液pH对普萘洛尔透皮性能的影响

Influence of pH on the Transdermal Performance of Propranolol Solution

关键词:  普萘洛尔  稳定性  离体透皮性能  lgP  酸碱度

Key words:  propranolol  stability  in vitro transdermal performance  lgP  pH

摘要:

目的 考察不同pH对普萘洛尔稳定性及离体透皮性能的影响。方法 采用HPLC测定普萘洛尔浓度；以4 500 lx光照及100 ℃高温进行加速试验，研究其在pH5.0～9.0内的稳定性；以正辛醇-磷酸盐缓冲液为模拟系统，采用摇瓶法测定不同pH下的lgP(油水分配系数的对数值)；并以大鼠腹部皮肤为模型，采用改良的Franz扩散池考察pH对药物透皮性能的影响。结果 普萘洛尔对热稳定，但在光照条件下发生降解，降解反应符合一级动力学过程，且具有明显的pH依赖性，表现为当pH高于7.4时降解速率常数显著增加。另外，普萘洛尔lgP随pH升高而增大，当pH在7.0以上时，lgP值均大于1，并表现出良好的透皮性能；当pH在7.0以下时，lgP及透皮性能均急剧下降。结论 本研究为普萘洛尔经皮给药制剂的设计与开发提供了实验依据。

Abstract:

OBJECTIVE To investigate the influence of pH on the stability and in vitro transdermal performance of propranolol. METHODS The concentration of propranolol was assayed by HPLC. The stability of propranolol solution accelerated with 4 500 lx light intensity or 100 ℃ with pH ranging from 5.0 to 9.0 was studied. The lgP in n-octanol－phosphate buffer solution(with variable pH) systems was determined by shaking flask method. The influence of pH on the transdermal efficiency through rat abdominal skin was estimated by utilizing the improved Franz diffusion cell. RESULTS Propranolol has good thermal stability, but degradation reaction happens when exposed to illumination. The degeneration reaction fits to first order kinetic model, and represents apparent pH-dependency. Besides, pH affects significantly both lgP and transdermal performance of propranolol. CONCLUSION The research provides experimental data for the design of transdermal delivery system of propranolol.