pH值对吡罗昔康理化性质及其经皮渗透性能的影响

目的:研究pH值对吡罗昔康理化性质及经皮渗透性能的影响,为其经皮给药制剂的研究提供实验依据。方法:用HPLC法测定药物在水、不同pH缓冲液(PBS)中的溶解度;采用双波长分光光度法测定药物的解离常数(pKa);摇瓶法测定药物的表观油水分配系数(logP);利用透皮扩散池以稳态渗透速率常数(Js)和通透系数(Ps)为评价指标研究药物的透皮效果。结果:吡罗昔康的pKa为6.33。32℃时,吡罗昔康在pH 7.4的缓冲液中logP为0.17,且溶解度和Js均达到最大,分别为(420.445)μg.mL-1和(64.612±0.011)μg.cm-2.h-1;Ps为(0.154±0.014)cm.h-1。结论:调节药物pH值,使药物维持较高的溶解度和分子型药物比例,可望获得理想的皮肤通透性。

Influence of pH on physico-chemical property and penetrable performance of piroxicam through rat skin

Objective: To determine the influence of pH on physico-chemical property of piroxicam and its percutaneous permeability.Methods: HPLC method was used to detect the solubility of piroxicam in water,and in various pH buffer solutions.Ambi-wavelength absorption spectrometry was used to determine the dissociation constant(pKa) of piroxicam.Shake-flask was used to determine the oil-water partition coefficient(logP) of piroxicam.The in vitro penetrable performance of piroxicam was evaluated by stable state permeation rate(Js) and permeability coefficient(Ps).Results: The pKa of piroxicam was 6.33.At 32℃,logP of piroxicam in the buffer of pH 7.4 was 0.17,in which its solubility and Js were the maximal,(420.445)μg·mL-1 and(64.612±0.011)μg·cm-2·h-1,respectively,compared with other pH values.The Ps of piroxicam in buffer of pH 7.4 was(0.154±0.014)cm·h-1.Conclusion: The adjusted pH can maintain a higher solubility and ratio of undissociated molecule of drug,which may be a promising means for improving percutaneous permeability of drug.