pH值对吡罗昔康理化性质及其经皮渗透性能的影响  

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

作　　者：于秋菊[1] 刘丽清[1] 谢茵[1] 石恩娴[1] 任国莲[1] 田青平[1] 

机构地区：[1]山西医科大学药学院,太原030001

出　　处：《中国新药杂志》2012年第4期443-447,共5页Chinese Journal of New Drugs

基　　金：山西医科大学博士启动基金(201003)

摘　　要：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。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.

关 键 词：吡罗昔康 表观溶解度 解离常数 油水分配系数 经皮渗透 

分 类 号：R943.43[医药卫生—药剂学] R971.1[医药卫生—药学]