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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。
Objective To investigate the effects of different pH on propranolol stability and in vitro transdermal performance. Methods The concentration of propranolol was determined by HPLC. The stability was tested at 4 500 lx light and 100 ℃. The stability of the solution was tested at pH 5.0 ~ 9.0. The n-octanol-phosphate buffer Shake-flask method was used to determine the lgP (logarithm of oil-water partition coefficient) at different pH values. The model of the abdominal skin of rats was used to investigate the effect of pH on the transdermal performance of the drug by using a modified Franz diffusion cell. Results Propranolol was stable to heat but degraded under light irradiation. The degradation reaction was in accordance with the first-order kinetic process with obvious pH dependence. The degradation rate constant increased remarkably when the pH was higher than 7.4. In addition, lpropylol lgP increased with increasing pH, when the pH above 7.0, lgP values ?? were greater than 1, and showed good transdermal properties; when the pH below 7.0, lgP and transdermal properties A sharp decline. Conclusion This study provides the experimental evidence for the design and development of propranolol transdermal drug delivery system.