采用平行人工渗透膜试验研究氨酚羟考酮片中对乙酰氨基酚和盐酸羟考酮的溶解性与渗透性  

Study on Biopharmacological Classification of Acetaminophen and Oxycodone HCl in Oxycodone and Acetaminophen Tablets by the Parallel Artificial Membrane Permeability Assay

作　　者：王文丽 张晓明 柯静 曲龙妹 田向斌 贺军权 WANG Wen-li;ZHANG Xiao-ming;KE Jing;QU Long-mei;TIAN Xiang-bin;HE Jun-quan(Gansu Institute for Drug Control,Lanzhou 730030,China;Yichang Renfu Pharmaceutical Co.,Ltd.,Yichang 443000,China)

机构地区：[1]甘肃省药品检验研究院,兰州730030 [2]宜昌人福药业有限责任公司,湖北宜昌443000

出　　处：《中国药学杂志》2021年第21期1735-1739,共5页Chinese Pharmaceutical Journal

基　　金：国家科技"重大新药创制"专项资助(2017ZX09101001);甘肃省药品科研项目资助(2020GSMPA016)。

摘　　要：目的采用平行人工膜渗透试验(PAMPA)对氨酚羟考酮片中的对乙酰氨基酚和盐酸羟考酮的有效渗透性进行研究,结合溶解性测定的结果,分析2种药物生物药剂学分类(BCS),为氨酚羟考酮片制剂的处方筛选与仿制药一致性评价提供参考。方法采用μFlux^(TM)型渗透测试系统测定2种药物和酒石酸美托洛尔在pH 5.0饱腹小肠模拟液(FeSSIF)和pH 6.5空腹小肠模拟液(FaSSIF)中的有效渗透性,结合2种药物在pH 1.0〜8.0缓冲溶液中的溶解度,分析BCS分类.结果在FeSSIF和FaSSIF中测定的有效渗透性,对乙酰氨基酚分别为2.22×10^(-6)和1.77×10^(-6)cm·s^(-1),盐酸羟考酮分别为30.8×10^(-6)和26.0×10^(-6)cm·s^(-1),酒石酸美托洛尔分别为9.62×10^(-6)和31.8×10^(-6)cm·s^(-1);对乙酰氨基酚和盐酸羟考酮溶解度分别为22.3~24.5和286.2~324.6 mg·mL^(-1)。结论与美托洛尔的有效渗透性比较,对乙酰氨基酚表现为“低渗透性”,盐酸羟考酮表现为“高渗透性”,2种药物均为“高溶解性”。对乙酰氨基酚为BCSⅢ类,盐酸羟考酮为BCSⅠ类。OBJECTIVE Parallel artificial membrane permeability assay(PAMPA)was used to study the effective permeability of acetaminophen and oxycodone HC1 in oxycodone-acetaminophen tablets combining with the determining results of the solubility of acetaminophen and oxycodone HC1,to analyze the biopharmaceutics classification system(BCS)of the drugs,which can provide reference for the formula optimization and quality consistency evaluation for generic drugs.METHODS TheμFlux^(TM)drug permeability test system was used to determine the effective permeability of acetaminophen,oxycodone HCl and metoprolol,measured in fed-state simulated intestinal fluid(FeSSIF,pH 5.0)and fasted-state simulated intestinal fluid(FaSSIF,pH 6.5),combining with the solubility of acetaminophen and oxycodone HCl in buffer solutions(pH 1.0〜8.0),the BCS classification of the drugs was analyzed.RESULTS The effective permeability measured in FeSSIF and FaSSIF were 2.22×10~6 cm·s^(-1)and 1.77×10^(-6)cm·s^(-1)for acetaminophen,30.8×1O-6 cm·s^(-1)and 26.0×10^(-6)cm·s^(-1)for oxycodone hydrochloride,9.62×10^(-6)cm·s^(-1)and 31.8×10^(-6)cm·s^(-1)for metoprolol tartrate,respectively.The solubilities of acetaminophen and oxycodone hydrochloride were 22.3 mg·mL^(-1)to 24.5 mg·mL^(-1)and 286.2 mg·mL^(-1)to 324.6 mg·mL^(-1),respectively.CONCOLUSION Compared with the effective permeability of metoprolol,acetaminophen is"low permeability",oxycodone hydrochloride is"high permeability",and both drugs are"high solubility".Acetaminophen belongs to BCSⅢ,while oxycodone hydrochloride belongs to BCSⅠ.

关 键 词：平行人工膜渗透试验 氨酚羟考酮 对乙酰氨基酚 盐酸羟考酮 渗透性 生物药剂学分类 

分 类 号：R944[医药卫生—药剂学]