苦参软膏体外释放评价方法的研究  

Investigation on evaluation method of in vitro release test for Kushen ointment

作　　者：凌霞 叶晓霞 张弢 方婧雯 乐健 LING Xia;YE Xiao-xia;ZHANG Tao;FANG Jing-wen;LE Jian(Shanghai Institute for Food and Drug Control,NMPA Key Laboratory for Quality Analysis of Chemical Drug Preparations,Shanghai 201203,China;Shanghai Baolong Pharmaceutical Co.,Ltd,Shanghai 201707,China;Shanghai University of Medicine&Health Sciences,Shanghai 201318,China)

机构地区：[1]上海市食品药品检验研究院、国家药品监督管理局化学药品制剂质量分析重点实验室,上海201203 [2]上海宝龙药业股份有限公司,上海201707 [3]上海健康医学院,上海201318

出　　处：《药物分析杂志》2023年第8期1408-1417,共10页Chinese Journal of Pharmaceutical Analysis

摘　　要：目的:建立苦参软膏体外释放评价方法,比较苦参软膏工艺变更前后的体外释放行为一致性。方法:采用改良Franz扩散池建立了软膏剂体外释放测定方法,以2020年版《中华人民共和国药典》苦参软膏含量测定项下的高效液相色谱方法为基础进行优化,建立苦参软膏释放量测定方法,评价不同处方工艺苦参软膏体外释放一致性。苦参软膏制剂主要释放氧化苦参碱、槐定碱、苦参碱和槐果碱4种活性成分。色谱柱采用Shim-pack GIS C_(18)柱(100 mm×4.6 mm,5μm),流动相A为乙腈,B为0.1%磷酸溶液(三乙胺调节pH至8.0),梯度洗脱,检测波长为210 nm,柱温为35℃,进样量为100μL,流速为2.0 mL·min^(-1)。结果:6批次苦参软膏样品均在18 h完全释放,释放量均>85%,工艺变更前后3批样品的释放速率分别为4058.9、4137.8、3873.6μg·cm^(-2)·h^(-1/2)和4177.9、4333.9、4389.1μg·cm^(-2)·h^(-1/2),工艺变更前后样品释放速率比值的90%标准置信区间为89.80%~102.94%,落在FDA一致性规定的75%~133.33%限度范围内;工艺变更前后样品累积释放曲线的f2相似因子为69.9,满足50≤f2≤100。结论:所建方法符合苦参软膏体外释放评价要求,处方工艺变更前后样品体外释放等效。Objective:To develop an evaluation method of in vitro release test for Kushen ointment and investigate the consistency of release behavior in pre-and post-manufacturing change of Kushen ointment.Methods:The modified Franz diffusion cell was employed for the in vitro release test of ointments.The dissolution was deter⁃mined by HPLC method based on the test of Kushen ointment in Chinese Pharmacopoeia(2020 edition).The consistency of release behavior of Kushen ointment varied with the formulation and preparation process was evalua⁃ted.The released drug substances included four active ingredients oxymatrine,sophoridine,matrine and sopho⁃carpine.Chromatographic separation was performed on a Shim-pack GIS C_(18)(100 mm×4.6 mm,5μm)col⁃umn using a mobile phase of acetonitrile(A)and 0.1%phosphoric acid solution(adjusted to pH 8.0 with triethylamine)(B)with a gradient elution.The detection wavelength was 210 nm,the column temperature was 35℃,the injection volume was 100μL,and the flow rate was 2.0 mL·min^(-1).Results:All 6 batches of Kush⁃en ointment samples were completely released at 18 h and the released amount were more than 85%.The in vitro release rate of 3 batches of Kushen ointment samples in pre-manufacturing change were 4058.9,4137.8 and 3873.6μg·cm^(-2)·h^(-1/2),respectively.The in vitro release rate of 3 batches of Kushen ointment samples in post-manufacturing change were 4177.9,4333.9 and 4389.1μg·cm^(-2)·h^(-1/2),respectively.The 90%con⁃fidence interval of the in vitro release rate of Kushen ointment samples in pre-and post-manufacturing change was 89.80%-102.94%within the quality consistency range from 75%to 133.33%defined by the FDA guide⁃line.The cumulative release curve similarity factor f2 between pre-and post-manufacturing change of Kushen ointment was 69.9 within the range from 50 to 100.Conclusion:The release behavior of Kushen ointment varia⁃tion with the formulation and preparation process was demonstrated to be quality consistent through the evaluation method of in vitro

关 键 词：苦参软膏 体外释放 仿制药一致性 改良Franz扩散池 液相色谱 

分 类 号：R917[医药卫生—药物分析学]