硫酸氨基葡萄糖固体口服制剂质量、企业执行标准评价及质控方法探索性研究  

Quality,enterprise implementation standards and quality control methods evaluation of glucosamine sulfate solid oral preparation

作　　者：王悦[1,2] 李俏吟 宋玉娟 程舒倩[1,2] 韩苗苗 范慧红 WANG Yue;LI Qiaoyin;SONG Yujuan;CHENG Shuqian;HAN Miaomiao;FAN Huihong(National Institutes for Food and Drug Control,Beijing 102629,China;NMPA Key Laboratory for Quality Research and Evaluation of Chemical Drugs,Beijing 102629,China)

机构地区：[1]中国食品药品检定研究院,北京102629 [2]国家药品监督管理局化学药品质量研究与评价重点实验室,北京102629

出　　处：《药物评价研究》2023年第11期2346-2353,2359,共9页Drug Evaluation Research

基　　金：青岛海洋科学与技术试点国家实验室海洋药物与生物制品功能实验室开放性课题(LMDBKF201806);中国食品药品检定研究院学科带头人培养基金(2021X6);化学药品质量研究与评价重点实验室学科建设课题(2023HYZX04)。

摘　　要：目的评价国内目前市售的硫酸氨基葡萄糖固体口服制剂的质量,考察现行标准中存在的问题,为生产和质量控制提供参考。方法对硫酸氨基葡萄糖固体口服制剂进行国家药品抽检(共73批,涉及8家生产企业),采用现行各企业执行的注册标准(共9个标准)对抽检样品进行法定检验。同时对产品进行探索性研究,表观溶解度参照《美国药典》(USP)1236通则;含量测定方法参照USP43硫酸氨基葡萄糖氯化钠项下相关方法;有关物质方法参照原研企业标准;囊壳铬含量测定方法按照《中国药典》2020年版明胶空心胶囊项下相关方法;建立近红外光谱一致性检验模型。结果73批次硫酸氨基葡萄糖制剂合格率97.3%,2批样品有关物质检查项目不合格。各家质量标准存在一定差异,个别企业质量标准不完善,有待提高,质量标准中部分重要项目检测方法待改进。此外,个别企业应考虑制剂配方工艺的合理性、包装材料的密封性和防潮措施等。探索性研究结果显示,目前各企业执行标准中均没有原料药溶解性检验,建议企业关注晶型等可能影响溶解度的因素;法定检验采用C8色谱柱的结果较探索性结果整体偏高,采用氯离子作为主成分峰进行含量控制方法不专属,紫外可见分光光度法操作复杂、结果偏差较大,建议改为更为简便和专属的HPLC法;原料药为非复盐的受试批次制剂的杂质检出种类、已知杂质果糖嗪和脱氧果糖嗪含量、其他已知杂质类别和总杂含量高于其他受试企业样品,推断原因为其易吸湿;泡腾片中果糖嗪含量较高,未知杂质数量多于其他剂型,推测原因为辅料较多;与胶囊剂相比,片剂含有的杂质更多,提示片剂生产过程中制粒、整粒等温度较高的步骤会对产品质量产生一定影响;可按生产厂家建立近红外光谱一致性模型或相关系数模型,补充本品的快速筛查方法。结论各企业质量�Objective To evaluate the quality of glucosamine sulfate solid oral preparations in China,and investigate the existing problems in the current standards,so as to provide reference for its production and quality control.Method The medicine post market quality surveillance of glucosamine sulfate solid oral preparations was conducted(73 batches in total,involving eight production enterprises).Use the current registration standards implemented by various enterprises(a total of nine standards)to conduct statutory inspections on sampled samples.At the same time,exploratory research was conducted on the product,with the apparent solubility referring to general rule 1236 of the United States Pharmacopoeia(USP).The content determination method shall refer to the relevant methods under USP43 glucosamine sulfate sodium chloride.Related substance methods refered to the standards of the original research enterprise for relevant material methods.The determination method for chromium content in the capsule shell shall be in accordance with the relevant methods under the gelatin hollow capsules section of the 2020 edition of the Chinese Pharmacopoeia.Establish a consistency testing model for near-infrared spectroscopy.Result The qualification rate of 73 batches of sulfated glucosamine preparations was 97.3%,and the relevant substance inspection items of two batches of samples are unqualified.There are certain differences in quality standards among different companies,and some companies have incomplete quality standards that need to be improved.The testing methods for some important items in the quality standards need to be improved.In addition,individual enterprises should consider the rationality of the formulation process,the sealing of packaging materials,and moisture-proof measures.The exploratory research results show that there was currently no testing for the solubility of raw materials in the execution standards of various enterprises.It is recommended that enterprises pay attention to factors such as crystal form that m

关 键 词：硫酸氨基葡萄糖 国家药品抽检 探索性研究 有关物质 现行标准 

分 类 号：R926[医药卫生—药学]