盐酸金霉素眼膏质量评价

Quality Evaluation of Chlortetracycline Hydrochloride Ointment

目的对盐酸金霉素眼膏制剂从安全性、有效性和质量可控性等方面,进行全面质量分析与评价并对质量标准进行完善。方法按国家计划性抽验工作总体要求,对国家药品计划抽验的210批次盐酸金霉素眼膏采用法定标准检验,并对有关物质、粒度、邻苯二甲酸酯类物质、多环芳烃、无菌工艺、药包材等项目开展了探索性研究。结果本次抽验盐酸金霉素眼膏210批次样品,采用法定标准检验,其中156批次合格,合格率为74.3%,54批次不符合规定,不合格率为25.7%,不合格项目均为粒度。探索性研究表明,不同厂家和不同批次产品间粒度差异较大,经显微拉曼测定,盐酸金霉素眼膏中超标粒子均为盐酸金霉素;有关物质、邻苯二甲酸酯类物质、多环芳烃不合格率较高,分别为32.5%、32.1%和18.9%,不合格率为44.8%;质量较差辅料凡士林中有多种有害成分含量较高且苯并[g,h,i]苝与邻苯二甲酸二丁酯(DBP)、邻苯二甲酸二异丁酯(DIBP)与邻苯二甲酸二辛酯(DEHP)检出量显著呈正相关;无菌保障方面存在质量风险隐患,应改进无菌生产工艺;部分铝管包装产品有“析油”现象,存在微生物污染风险。结论综合法定标准检验与探索性研究实验,盐酸金霉素眼膏盐酸金霉素眼膏现行标准基本可行,质量状况有待进一步改善。粒度不合格、辅料质量、无菌保障是影响本产品质量的关键因素,建议相关企业严格控制原料质量、改进生产工艺以无菌原料投料,加强对凡士林等辅料质量的监管。建议对该品种质量标准进行完善,确保标准可控。

OBJECTIVE To conduct a comprehensive quality analysis and evaluation of chlortetracycline hydrochloride ointment from the aspects of safety,effectiveness and quality controllability,and perfect the quality standards.METHODS In accordance with the overall requirements of the national planned random inspection work,210 batches of chlortetracycline hydrochloride eye ointment sampled by the National Drug Inspection Plan were tested using legal standards.Exploratory research was carried out on related substances,particle size,phthalates,polycyclic aromatic hydrocarbons,aseptic technology,pharmaceutical packaging materials and other test items.RESULTS Among the 210 batches of chlortetracycline hydrochloride eye ointment 156 batches passed the legal standards,indicating a pass rate of 74.3%;54 batches did not comply with the regulations,resulting an unqualified rate of 25.7%,and the unqualified items were all granularity.Exploratory research showed that the particle size difference among different manufacturers and different batches of products was large.As shown by the micro-Raman measurement,the particles exceeding the limit in chlortetracycline hydrochloride ointment were chlortetracycline hydrochloride.The relevant materials,phthalates,and polycyclic aromatic hydrocarbons had high unqualified rates,32.5%,32.1%,and 18.9%,respectively,and the total failure rate of exploratory research was 44.8%.Poor quality vaseline contained a variety of harmful ingredients with high content and benzo[g,h,i]perylene was significantly positively correlated with dibutyl phthalate(DBP),diisobutyl phthalate(DIBP)and diethylhexyl phthalate(DEHP).There were major defects and hidden quality risks in sterility guarantee,and the aseptic production process should be improved.Some aluminum tube packaging products had the phenomenon of"oil separation"and there was a risk of microbial contamination.CONCLUSION Based on comprehensive legal standard inspection and exploratory experiments,the current standard of chlortetracycline hydrochloride ointment is basically feasible.Particle size,quality of excipients,and sterility guarantee are the key factors affecting the quality of this product.It is recommended that relevant manufacturers strictly control the quality of raw materials and improve production processes and strengthen the supervision of the quality of petrolatum and other excipients.It is also recommended to improve the quality standards of this product to ensure that the standards are controllable.