盐酸羟考酮缓释片体外释药特性研究  

Study on the in Vitro Release Characteristics of Oxycodone Hydrochloride Sustained-Release Tablets

作　　者：刘新颖 许向阳 曾令高 毛文星 郑冬梅 高梓真[1] LIU Xinying;XU Xiangyang;ZENG Linggao;MAO Wenxing;ZHENG Dongmei;GAO Zizhen(Pharmaceutical Research Institute of Jiangsu Nhwa Pharmaceutical Co.,Ltd.·Jiangsu Provincial Key Laboratory of Central Nervous System Drug,Xuzhou,Jiangsu,China 221000;Chongqing Institute for Food and Drug Control·NMPA Key Laboratory for Quality Monitoring of Narcotic Drugs and Psychotropic Substances,Chongqing,China 401120)

机构地区：[1]江苏恩华药业股份有限公司药物研究院·江苏省中枢神经药物研究重点实验室,江苏徐州221000 [2]重庆市食品药品检验检测研究院·国家药品监督管理局麻醉精神药品质量监测重点实验室,重庆401120

出　　处：《中国药业》2023年第16期52-56,共5页China Pharmaceuticals

基　　金：国家药品监督管理局麻醉精神药品监测重点实验室开放课题[NPKF-2021-01];重庆英才计划“包干制”项目[cstc2021ycjh-bgzxm0315]。

摘　　要：目的研究盐酸羟考酮缓释片的体外释药特性。方法采用篮法进行溶出试验,分别测定盐酸羟考酮缓释片在pH 1.2氯化钠盐酸溶液、pH 4.5醋酸盐溶液、pH 6.8磷酸盐溶液介质中的溶出度,并作溶出曲线,对体外溶出曲线进行模型拟合,考察其释放动力学及释药机制;采用往复筒法进行溶出试验,对往复筒的关键设置参数进行考察。测定样品在含不同体积分数(0,5%,20%,40%)乙醇pH 1.2盐酸介质的溶出度,并作溶出曲线,评估剂量倾泻风险。结果盐酸羟考酮缓释片的体外释放呈一级动力学,释药机制为溶蚀与扩散相结合;往复频率与溶出速率呈正相关,筛网规格在20~40目之间对溶出行为的影响较小。且乙醇不会导致剂量倾泻。结论本研究中分别建立了篮法及往复筒法测定盐酸羟考酮缓释片体外溶出度,可为体外溶出评价提供更多的评估手段。并建立了体外溶出曲线模型拟合及乙醇剂量倾泻实验方法,为了解该药体外释放规律及行为提供了更多参考。Objective To study the in vitro release characteristics of Oxycodone Hydrochloride Sustained-Release Tablets.Methods The basket method was used to determine the dissolution of Oxycodone Hydrochloride Sustained-Release Tablets in sodium chloride-hydrochloric acid solution(pH 1.2),acetate buffer solution(pH 4.5)and phosphate buffer solution(pH 6.8),respectively.The dissolution profiles were made,and its release kinetics and release mechanism were investigated by the model fitting of in vitro dissolution profiles.The reciprocating cylinder method was used for dissolution test,and the key setting parameters of reciprocating cylinder were investigated.The dissolution of Oxycodone Hydrochloride Sustained-Release Tablets in hydrochloric acid solution(pH 1.2)containing ethanol with different volume fractions(0,5%,20%,40%)was determined,and the dissolution profiles were made to assess the risk of dose dumping.Results The in vitro release of Oxycodone Hydrochloride Sustained-Release Tablets was corresponded with the characteristics of first-order kinetics,and the release mechanism was a combination of corrosion and diffusion.The reciprocating frequency was positively correlated with the dissolution rate,and the sieve size in the range of 20 to 40 mesh had little effect on the dissolution behavior.Ethanol did not induce the dose dumping.Conclusion We have established the basket method and the reciprocating cylinder method to determine the in vitro dissolution of Oxycodone Hydrochloride Sustained-Release Tablets in this study,which can provide a basis for the in vitro dissolution evaluation.We also carry out model fitting of in vitro dissolution profiles and dose dumping research of ethanol,which can provide a reference for explaining the in vitro release law and behavior of this drug.

关 键 词：盐酸羟考酮缓释片 溶出曲线 模型拟合 剂量倾泻 篮法 往复筒法 体外释药特性 

分 类 号：R917[医药卫生—药物分析学] R97[医药卫生—药学]