盐酸羟考酮缓释片体外一致性评价研究

Study on Consistency Evaluation of in Vitro Oxycodone Hydrochloride Extended-release Tablets

关键词:  盐酸羟考酮缓释片  释放曲线  有关物质  一致性评价

Key words:  oxycodone hydrochloride extended-release tablets  dissolution curve  related substance  consistency evaluation

摘要:

目的 建立盐酸羟考酮缓释片释放曲线测定方法和有关物质检测方法，评价自制制剂和原研制剂释放曲线的相似性和有关物质杂质谱的一致性。方法 用4种释放介质[水、盐酸（pH 1.2）、乙酸盐缓冲液（pH 4.0）和磷酸盐缓冲液（pH 6.8）]分别考察自制盐酸羟考酮缓释片和原研制剂的释放情况，并通过计算相似因子（f₂）评价溶出曲线的相似性；优化有关物质检查色谱条件，使14-羟可待因酮、氢可酮达到基线分离，对比研究自制盐酸羟考酮缓释片与原研制剂的有关物质，进行杂质谱研究。结果 自制制剂与原研制剂在4种释放介质中释放曲线的f₂均>50，表明2种制剂体外释放行为相似，且两者的有关物质杂质谱基本一致，表明2种制剂质量基本一致。结论 建立的释放曲线、有关物质测定方法准确、可靠，可为盐酸羟考酮缓释片的仿制药一致性评价提供参考。

Abstract:

OBJECTIVE To establish a new method for the dissolution curve determination and related substance of oxycodone hydrochloride extended-release tablets,and evaluate the comparability of dissolution curve and the related substances of the self-made oxycodone hydrochloride extended-release tablets and the original drug. METHODS The dissolution curves of two preparations in four media, including water, hydrochloric acid(pH 1.2), acetate buffer solution(pH 4.0) and phosphate buffer solution(pH 6.8), were made, and their similarity was evaluted by similarity factor. The chromatographic conditions of the related substances were optimized and the baseline separation of 14-hydrocodine ketone and hydrocodone was achieved. The related substances of self-made oxycodone hydrochloride sustained-release tablets and reference preparetions were compared and the impurity profile was studied. RESULTS The similarity factor of the release curves of the self-made drugs and the original drugs in four release mediums was>50, which indicated that the release behavior of the two preparations in vitro was similar, and the mass spectra of the related substances of the two preparations were basically the same, indicated that the quality of the two preparations was basically the same. CONCLUSION The established release curve and determination method of related substances are accurate and reliable, which can provide reference for the consistency evaluation of generic drugs for oxycodone hydrochloride extended-release tablets.