乙酰氨基阿维菌素注射用缓释剂质量标准与药学等效研究

Study on Quality Standard and Pharmaceutical Equivalence of Eprinomectin Sustain-release Injections

依据《中华人民共和国兽药典》与《兽药研究技术指导原则汇编》等相关指导要求,对乙酰氨基阿维菌素(EPR)注射用缓释剂进行外观、黏度、pH、水分、密度、内毒素、含量及有关物质检测,建立EPR注射用缓释剂的质量标准并比较与参比制剂的药学等效性。含量与有关物质检测方法为使用ZORBAX Eclipse Plus C18柱(2.1 mm×50 mm,1.8μm);流动相:甲酸∶水∶乙腈(0.04 mL∶40 mL∶60 mL);流速:0.4 mL/min;检测波长:245 nm;柱温:35℃;进样量:2μL。在37℃,转速为50 r/min,0.5%SDS的PBS缓冲液条件下,比较自研与原研EPR注射用缓释剂的药学等效性。EPR注射用缓释剂外观澄清透明,平均相对黏度为46.45 mPa·s,平均pH为6.88,制剂中不含水分,密度为1.13 g/cm^(3),内毒素满足<0.1 EU/mL限度,含量>5%的标示值,有关物质的量<5%,检测结果均符合注射剂制剂要求;在同一条件下释放31 d后,自研与原研EPR注射用缓释剂累积释放量均超过80%,且自研与原研的相似因子(f2)值>50。自研EPR注射用缓释剂的检测结果均符合注射剂标准,自研与原研EPR注射用缓释剂具有药学等效。

Following the Veterinary Pharmacopoeia of the People’s Republic of China and The Compendium of Technical Guidelines for Research on Veterinary Drugs,the appearance,viscosity,pH,moisture,density,endotoxin,content and releated-substances tests were carried out on eprinomectin(EPR)extended-release injection agent to establish the quality standard and compare the pharmacological equivalence with the reference formulation.Content and related substances were determined on ZORBAX Eclipse Plus C18 column(2.1 mm×50 mm,1.8μm),mobile phase:formic acid∶water∶acetonitrile(0.04 mL∶40 mL∶60 mL);Flow rate:0.4 mL/min;Detection wavelength:245 nm;Column temperature:35℃;Injection volume:2μL.The pharmacological equivalence of the agent(f2 value)was calculated by comparing the release degree under the conditions of PBS buffer of 0.5%SDS at 37℃and the rotation speed of 50 r/min.After testing,the appearance of EPR sustained-release injection agent was clear and transparent,the average relative viscosity was 46.45 mPa·s,the average pH was 6.88,the preparation did not contain water,the density was 1.13 g/cm^(3),the endotoxin met the limit of less than 0.1 EU/mL,the content was greater than the labeled value of 5%,the amount of the substance was less than 5%,the test results were all in line with the injectable preparation requirements.After 31 d of release under the same conditions,both self-research and the original EPR sustained-release injection agent release were more than 80%,and the f2 value of self-research and the original was more than 50.The test results of self-researched EPR sustained-release injection agent were all in accordance with the standard for injectable agents,and the self-researched and original EPR sustained-release injection agent were pharmacologically equivalent.