磷酸咯萘啶胶囊的质量研究

The Quality Control of the Malaridine Phosphate Capsule

摘要: 疟疾(malaria)是由疟原虫经按蚊叮咬传播的污染病。临床上以周期性定时性发作的寒战、高热、出汗退热及贫血和脾大为特点。疟疾仍然是国际上十大传染病之一，据统计每年发病人数为3~5亿，死于疟疾者约百万人。咯萘啶是70年代初合成抗疟新药，临床上主要以四磷酸盐形式存在。本文确定磷酸咯萘啶胶囊新药处方、生产工艺、建立质量标准、中试生产并检测、进行加速和长期稳定性考察、研究药理毒理药效药代学等。采用正交试验法、流体力学、休止角研究和制药技术确定最佳处方及工艺，建立了HPLC和UV进行控制质量方法；在国家GMP车间内进行中试规模化生产并检测，采用市售包装于40℃相对湿度75% ± 5%及25℃相对湿度60% ± 5%条件下按新药稳定性指导原则分别取样，检测其外观、有关物质、溶出度及含量。处方合理，工艺简便可行。制定质量标准和检测方法，产品质量稳定有效期长为2年。解决了常规制剂的不足和生物利用度低的缺点，具有明显的经济效益和社会效益。

Abstract: Malaria is an infectious disease which is spread by mosquitoes biting. Its features are shiver, high fever, sweating defervescence, anemia and splenomegalia. Malaria remains one of the ten largest infectious diseases globally. According to statistics, 300 - 500 million people are infected by malaria and 1 million people are died of malaria annually. The new anti-malarial medicine synthesized at the beginning of 1970s exists in the form of tetraphosphate clinically. This paper is to determine the prescription and production process of new drug—Malaridine Phosphate Capsule, establish quality standards, perform pilot scale production and detection, carry out acceleration and long-term stability investigation and research pharmacology, toxicology, pharmaceutical effect, pharmacokinetics, etc. It is to determine the optimum prescription and process by orthogonal test, hydromechanics, angle of repose research and pharmaceutical technology. It is to build quali-ty-control method by HPLC and UV; to perform pilot large-scale production and detection in national GMP workshop, detect the appearance, related substances, dissolution rate and content of commercially available packages by sampling in 40˚C, 40% relative humidity and 25% ± 5%, 60% ± 5% relative humidity respectively according to new drug stability guiding principle. Conclusion: 1) Reasonable prescription. 2) Simple and feasible process. 3) Quality standards and detection method have been established. 4) 2-year of stable-quality expiry date. 5) Obvious economical and social benefits instead of inadequate conventional formulations and bioavailability.