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

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.