磷酸咯萘啶胶囊的质量研究
The Quality Control of the Malaridine Phosphate Capsule

作者: 王洪杰 :格特生物制药(天津)有限公司,天津;

关键词: 磷酸咯萘啶胶囊处方工艺稳定性Malaridine Phosphate Capsule Prescription Craft Stability

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.

文章引用: 王洪杰 (2015) 磷酸咯萘啶胶囊的质量研究。 药物资讯, 4, 1-14. doi: 10.12677/PI.2015.41001

参考文献

[1] 丁雪 (2008) 21中国疟疾流行现状综述. 中华流行病学杂志, 2, 112-113.

[2] Cheng, C. and Zheng, X.Y. (1992) Development of the new antimalarial pyronaridine: A review. Biomedical and Environmental Sciences, 5, 149-160.

[3] Pascal, R., Jean, B. and Leonardo, K. (1996) BASCO in vitro activity of antimalarials clinical isolates of plasmodium falciparum in Yaounde. The American Journal of Tropical Medicine and Hygiene, 55, 254-258.

[4] Ringwald, P., Bickii, J., Same-Ekobo, A. and Basco, L.K. (1997) Pyronaridine for Treatment of Plas-modium ovale and Plasmodium malariae Infections. Antimicrobial Agents and Chemotherapy, 41, 2317-2319.

[5] 上海医药工业研究院药物制剂部、药物制剂国家工程研究中心编著 (2002) 药物辅料应用技术. 第二版, 中国医药科技出版社, 北京.

[6] 罗明生主编 (1995) 药剂辅料大全. 四川科学技术出版社, 成都.

[7] (2010) 中国药典2010年版二部.

[8] 奚念朱主编 (1980) 药剂学. 第三版, 人民卫生出版社出版, 北京, 休止角测定法1.

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