盐酸羟考酮缓释片的制备及防滥用性能评估  

Preparation of Oxycodone Hydrochloride Extended-Release Tablets and Evaluation of Their Abuse-Deterrent Properties

作　　者：王佳瑜[1] 高梓真[1] 许向阳 刘新颖 毛文星 曾令高 WANG Jiayu;GAO Zizhen;XU Xiangyang;LIU Xinying;MAO Wenxing;ZENG Linggao(Pharmaceutical Research Institute of Jiangsu Nhwa Pharmaceutical Co.,Ltd.,Jiangsu Provincial Key Laboratory of Central Nervous System Drugs,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 401121)

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401121

出　　处：《中国药业》2023年第19期17-21,共5页China Pharmaceuticals

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

摘　　要：目的筛选盐酸羟考酮缓释片(防滥用剂型,以下简称自研制剂)的制剂处方,评估其防滥用性能。方法以流变仪检测黏度为指标,对处方中抗氧剂、聚氧乙烯(PEO)进行筛选;采用热熔挤出技术制备自研制剂,以OxyContin■为参比制剂进行防滥用特性(包括溶出度、凝胶强度、可注射性、硬度、粉碎后粒度分布)及可提取性的比较。结果优选处方中,WSR N750(相对分子质量为300000)与WSR 303(相对分子质量为7000000)的比例为1∶6(m/m),抗氧剂为0.10%维生素E。与参比制剂比较,相似因子(f_(2))为80.02,两者的体外释放行为相似;硬度更大,粉碎后细颗粒更少,更难被物理破坏,凝胶强度更高,可注射性更差;在水、40%乙醇溶液、无水乙醇、异丙醇中90 min内可提取率相当。结论采用热熔挤出技术制备的自研制剂的防滥用特性优于参比制剂,可为后续仿制药的研究提供参考。Objective To screen the formulation prescription of Hydrochloride Extended-Release Tablets(abuse-deterrent formulations,hereinafter referred to as self-developed formulations),and to evaluate their abuse-deterrent properties.Methods The antioxidant and polyethylene oxide(PEO) in the prescription were selected with the viscosity detected by rheometer as an index.The self-developed formulations were prepared by hot-melt extrusion(HME) technology,and the differences in the abuse-deterrent properties(including dissolution rate,gel strength,injectability,hardness,particle size after crushing),and extractability of the self-developed formulations were compared with those of OxyContin■ reference preparation.Results The preferred formulation had a 1∶6(m/m)ratio of WSR N750(relative molecular weight of 300 000)to WSR 303(relative molecular weight of 7 000 000),with the antioxidant of 0.10% vitamin E.Compared with the reference preparation,the similarity factor(f_(2)) value of preferred formulation was 80.02,and both had similar in vitro release behaviors;the preferred formulation was much harder,with fewer fine particles after pulverization,and was more difficult to be physically destroyed.Meanwhile,it had a higher gel strength and poorer injectable fluidity.The extractability of the preferred formulation in water,40% ethanol,anhydrous ethanol,and isopropanol for 90 min was comparable to that of the reference preparation.Conclusion The abuse-deterrent properties of self-developed formulations prepared by HME technology were better than those of the reference preparation,which can provide a reference for the subsequent study of generic drugs.

关 键 词：盐酸羟考酮缓释片 热熔挤出技术 防滥用性能 仿制药 

分 类 号：R927.1[医药卫生—药学] R971