基于国家评价性抽检的盐酸丙卡特罗片质量分析与研究

Quality Analysis and Study on Procaterol Hydrochloride Tablets on National Drug Evaluation Sampling Inspection

目的:通过对国内上市的盐酸丙卡特罗片的检验及研究,从安全性、有效性、刻痕及质量可控性等方面对其进行全面质量分析评价,进一步完善质量标准。方法:按照现行质量标准对盐酸丙卡特罗片进行法定检验,查阅国内外标准及文献,赴生产企业实地调研,开展有关物质、金属元素、崩解行为、溶出度与溶出曲线和刻痕等5个方面的探索研究。结果:111批次样品按标准检验,合格率为100%;在探索性研究中,新建了有关物质测定法,样品中的杂质量普遍偏高且与金属元素和水分的含量基本呈正相关,杂质主要来源于制剂和贮藏过程;采用应用视觉技术对各企业样品及原研制剂在水中的崩解行为及时间进行考察,所有样品均在3 min内全部崩解;参照日本橙皮书将小杯法修订为桨法,考察各企业样品的溶出度及在4种介质中的溶出曲线,以原研制剂为参比品,考察结果相似,除1家企业的样品因为原辅料不相容引起主药在水中降解外,其余样品的溶出量均在15 min达到85%;参比制剂和部分国产样品带有中间刻线,半片均匀度结果表明均为非功能性刻痕,另半片在无内包装放置24 h后稳定性差。结论:现行标准中缺少有关物质检查项,亟待完善;样品的安全性风险较大,功能性刻痕有待完善。

Objective: Through the inspection and study of domestic-listed procatrol hydrochloride tablets, the comprehensive quality analysis and evaluation were carried out in the respects of safety, effectiveness, notch and quality controllability in order to further improve the quality standard. Methods: According to the current quality standard, the legal inspection of procatterol hydrochloride tablets was carried out, the domestic and foreign standards and literature were consulted, the field investigation in the production enterprises was conducted, and the researches on related substances, metal elements, disintegration behavior, dissolution, dissolution curve and notch have been done. Results: The qualified rate of 111 batches of samples was 100%. In the exploratory study, a new method for determination of related substances was established. The impurities in the samples were generally high and positively correlated with the content of metal elements and moisture. The impurities mainly came from preparations and storage processes. The disintegration behavior and time of samples and original preparation in water were investigated by using visual technology. All samples disintegrated within 3 minutes;Referring to the Japanese Orange Book, the small cup method was revised to be paddle method, and the dissolution and dissolution curves of samples from various enterprises in four media were investigated.The results were similar with the original preparation as a reference. Except for one case where the sample of one enterprise caused the main drug to degrade in water due to incompatibility of raw auxiliary materials, the dissolution amount of the other samples have reached into 85% within 15 min. The reference preparation and some domestic samples have intermediate score lines, and the uniformity results of half tablets show that they can not be effectively divided, and the stability of the other half tablets is poor after being placed without inner packaging for 24 hours. Conclusion: The relevant substances in the current standards are missing and need to be improved urgently. The safety risks of the samples are greater, and the functional scores need to be improved.