摘要
目的探讨化学药口服固体制剂变更原料药供应商的研究流程。方法以苯磺酸氨氯地平片变更原料药供应商为例,考察变更后原料药的晶型、粒度分布、有机杂质、残留溶剂、致突变杂质、元素杂质;利用变更后的原料药制备3批小试样品,考察在0.01 mol/L盐酸溶液、pH 4.0醋酸盐缓冲液、pH 5.5磷酸盐缓冲液、pH 6.8磷酸盐缓冲液中的溶出曲线;进行3批工艺验证,比较原料药供应商变更前后样品中有关物质、含量均匀度、溶出度、含量等制剂关键质量指标的差异,并考察溶出曲线。结果供应商变更后,原料药粒度D_(50)为9~10μm,D_(90)为20~23μm;晶型、有机杂质基本一致;均未检出残留溶剂、致突变杂质;元素杂质含量测定结果均符合规定。3批小试样品在4种溶出介质中的溶出曲线与参比制剂和生物等效(BE)批制剂的溶出曲线均一致。3批工艺验证样品的含量、含量均匀度、溶出度分别为99.7%~99.9%、5.8%~5.9%、97%~100%,均不低于变更前的98.3%~99.5%、5.3%~5.8%、97%~99%;有关物质中,杂质D含量均为0.04%,低于变更前的0.06%~0.10%。结论基于苯磺酸氨氯地平片变更原料药供应商质量研究,初步建立了化学药口服固体制剂变更原料药供应商研究的基本流程。
Objective To investigate the research process of changing the supplier of active pharmaceutical ingredients(API)for oral solid preparation of chemical drugs.Methods Taking the change of API supplier for Amlodipine Besylate Tablets as an example,the crystal form,distribution of particle size,organic impurities,residual solvents,mutagenic impurities,and elemental impurities of the changed API were investigated.Three batches of small test samples were prepared by the changed API,and their dissolution profiles were determined in 0.01 mol/L hydrochloric acid solution,pH 4.0 acetate buffer,pH 5.5 phosphate buffer,and pH 6.8 phosphate buffer.Three batches of processes were validated,and the differences in key quality-related indicators(such as related substances,content uniformity,dissolution rate,and content)of the preparation were compared in the samples before and after the change of the API supplier,and the dissolution profiles were determined.Results After the change of API supplier,the particle size D_(50) of the API was in the range of 9-10μm,and D_(90) was in the range of 20-23μm;the crystal form and organic impurities were basically consistent with those before the change;no residual solvents or mutagenic impurities were detected;the content determination results of elemental impurity all met the regulations.The dissolution profiles of three batches of small test samples were consistent with those of the reference preparation and bioequivalent(BE)batch preparation in the four dissolution media.The content,content uniformity,and dissolution rate of the three batches of process validation samples were 99.7%-99.9%,5.8%-5.9%,and 97%-100%,respectively,which were not lower than 98.3%-99.5%,5.3%-5.8%,and 97%-99%before the change.In the relevant substances,the content of impurity D was 0.04%,which was lower than the 0.06%-0.10%before the change.Conclusion Based on the quality study of the change of API supplier for Amlodipine Besylate Tablets,a basic research process of changing the API supplier for oral solid preparation of chemical drugs has been preliminarily established.
作者
王燕敏
WANG Yanmin(Sinopharm RonShyn Pharmaceutical Co.,Ltd.,Jiaozuo,Henan,China 454950)
出处
《中国药业》
CAS
2023年第21期73-79,共7页
China Pharmaceuticals
关键词
苯磺酸氨氯地平片
化学药
口服固体制剂
药物活性成分
供应商变更
药品监管
Amlodipine Besylate Tablets
chemical drugs
oral solid preparations
active pharmaceutical ingredients
changes of suppliers
drug administration