论文总字数：17269字

摘 要

保泰松是一类具有抗炎效果很强的药物，对于治疗炎性疼痛效果较好，用于风湿性关节炎及痛风,类风湿性关节炎的治疗。由丙二酸二乙酯、甲醇钠、氢化偶氮苯、乙醇钠、正丁醇等上游原料合成。药品微粉是药物粒径缩小到一定程度,可以增加药品的表面积,从而增加与细胞的有效接触面,促进药品溶解于人体内,便于药品的调配、服用和发挥药效,便于药品的干燥和储藏。气流粉碎技术发展成熟,生产能力高,成本较低,用于药物粉碎具有粒径控制便捷、操作简单、无污染、低温性、保持原有晶体形态和性状、符合GMP规范要求等特点,特别适合于药品微粉的加工。实际上目前国内外基本采取气流粉碎机对药物的微粉化进行加工。本论文对于气流粉碎机进行了拆卸和清洁，并对其进行取样和清洁验证。清洁验证包括了回收率的测定、API药品残留和微生物含量的测定，回收率测定是取样方法的有效性和重现性的一种表现,残留检测是对符合GMP清洁设备的药品及微生物残留的检验,是药企安全生产的保障。清洁验证的意义就是通过科学的方法采集足够的数据和资料,以表明按规程清洁后的气流粉碎机,能够达到预定的清洁标准,从而可以持续进行安全有效的规模化生产工作。

关键词：保泰松 清洁验证 微粉 回收率

ABSTRACT

Bute is a class of drugs with anti-inflammatory effect is very strong,Has good effect in treating inflammatory pain,Used in rheumatoid arthritis and gout, the treatment of rheumatoid arthritis.From diethyl malonate, sodium methoxide, sodium hydride azo benzene, ethanol, n-butyl alcohol upstream raw materials synthesis.Micro powderIs the drug powder particle size reduced to a certain degree,Can increase the surface area of the drug,To increase the effective contact area of cell,Promote the dissolution of drug in the body,To facilitate the deployment of drugs, the taking and exert efficacy, ease of drying and storage of the drug.Airflow smashing technology development mature, high production capacity, low cost,With particle size control convenient, simple operation, no pollution, low temperature resistance, keeping the original crystal morphology and properties, conform to the requirements of GMP and other characteristics ,Suitable for drug powder processing.In fact basic take jet mill at home and abroad for processing of drug micronization..In this paper to remove and clean airflow crusher, and carries on the sampling and cleaning validation.Cleaning validation, including the determination of the recovery, API and drug residues and the amount of microorganism, recovery rate determination is the validity of the method of sampling and reproducibility of a performance, clean residue detection is to meet the requirements of GMP medicines and microbial residues of inspection equipment, is the guarantee of medicine enterprise safe production.Cleaning validation is through the significance of the scientific method to collect enough data and information, to indicate that according to the regulations of jet mill after cleaning, can achieve predetermined cleaning standards, thus can continue mass production of safety work.

KEYWORDS: phenylbutazone ; cleaning validation recovery percent ; micro powder; Residue detection

目 录

摘 要 I

ABSTRACT II

目 录 IV

第一章文献综述 1

1.1引言 1

1.2保泰松的介绍 1

1.2.1保泰松的性质 1

1.2 .2药理作用 1

1.2.3不良反应及相互作用 1

1.3药品的微粉化 2

1.3.1微粉药物介绍 2

1.3.2 粉体制备技术 2

1.3.3 微粉制备技术分析 3

1.3.4 药物微粉制备技术发展趋势 4

1.4药品残留检测概述 4

1.4.1取样点的选择原则 4

1.4.2擦拭取样方法 5

1.4.3擦拭取样法的优劣 5

1.4.4擦拭工具和溶剂选择 5

1.4.5直接表面取样 6

1.5取样回收率测定的意义 6

1.6 API残留 6

1.7本课题的目的与意义 7

第二章 材料、设备与方法 8

2.1 实验材料 8

2.1.1 实验试剂 8

2.1.2 实验器材 8

2.1.3 培养基 8

2.2实验内容及方法 9

2.2.1清洁气流粉碎机 9

2.2.2取样 9

2.2.3线性测定 10

2.2.4回收率测定 11

2.2.5 API残留量分析 11

2.2.6微生物检验 11

2.2.7微粉化保泰松 11

第三章 实验结果与讨论 12

3.1线性测定 12

3.2回收率测定(限度10ug/ml) 13

3.3API残留测定 13

3.4微生物菌落检测 14

3.5保泰松粒径测试 16

第四章 结论与展望 18

参考文献 19

致 谢 22

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