氨苯喋啶片质量分析

Quality analysis on Triamterene Tablets

目的对氨苯喋啶片101批样品进行法定标准检验及探索性研究,对该品种的质量状况作出总体分析及评价。方法法定标准检验依据《中国药典》2010年版二部,其质量标准设定有性状、化学反应鉴别、溶出度、重量差异、UV法测定含量。探索性研究参照BP2010年版氨苯蝶啶原料项下有关物质检测方法,采用优化后的HPLC法考察各企业提供的氨苯蝶啶原料及101批片剂中的有关物质;采用HPLC法测定5个企业的样品在4种不同pH值介质中的溶出曲线,并与日本橙皮书中氨苯喋啶片溶出曲线进行比较;建立了溶出度测定的非标方法,并对全部样品进行检验;为考察辅料及各有关物质对氨苯蝶啶含量测定的影响,建立了HPLC法测定氨苯蝶啶片含量的方法。结果法定标准检验:101批样品,5批次不符合规定,不合格率为5%,不合格项目均为溶出度检查。探索性研究:有关物质研究表明制剂中的杂质来源于原料,检验101批样品,均检出已知杂质B、C和一个未知杂质,均未检出已知杂质A;溶出曲线及溶出度研究比较了该制剂在4种不同pH值介质中的溶出曲线,5家生产企业制剂溶出曲线与日本橙皮书上的相似性差异大,有3家生产企业的自身批间均一性相对较好;含量测定结果说明辅料及各有关物质对氨苯蝶啶含量测定基本无影响。结论各生产企业氨苯蝶啶片的质量参差不齐,总体质量状况与日本药品有差距,建议进一步进行生物等效性研究,改进制剂工艺,提高质量。

Objective The quality overall analysis and evaluation were made through the combination of mandatory standard inspection and exploratory research of 101 batches of Triamterene Tablet samples. Methods Mandatory standard inspection： pursuant to the Chinese Pharmacopoeia 2010, the quality standard consisted of properties, chemical reaction identification, dissolution rate, weight variation, and UV spectrometry content. Exploratory research： with reference of Triamterene raw material relative testing method of BP 2010, the optimized HPLC method was employed to inspect the relative materials of producers provided triameterene raw materials and 101 batches of Triamterene Tablets. The PHLC method was employed to achieve the dissolution curves of five producers provided Triamterene samples in four media with different pH values. The comparison among those dissolution curves with the ones of Japan Orangebook was made accordingly. The non-standard method of Triamterene was established and applied to inspect all samples. To investigate the influence of auxiliary materials and relevant materials in triamterene, the PHLC was developed for the determinatin of triamterene content in Triamterene Tablets. Results Mandatory standard inspection： among 101 batches of sample, five batches were inconformity, the fraction defective was about 5%, the unqualified item was dissolution inspection. Exploratory research： in the relevant material research, 101 batches of sample were inspected, all samples were detected with known impurity B, C, and a unknown impurity, no known impurity A found. Dissolution curve and dissolution rate research： to compare the dissolution curves of preparations in four media with different pH value, the dissolution curves from five producers＇ preparation have the apparent similar difference with the ones of Japan Orangebook, while the inter-batch uniformity of three producers＇ products was relative good. The result of the content inspection indicated that the auxiliary materials and relevant materials were with no apparent influence on the triamterene content inspection. Conclusion The quality of Triamterene Tablets from the individual producer are uneven, while the overall quality is lower than that of Japanese product. It is suggested to enhance the pharmaceutical bioequivalence study, innovate the pharmaceutical technology, and to improve the quality accordingly.