氨甲环酸缓释片的制备和质量标准研究

发布时间：2018-06-04 22:52

本文选题：氨甲环酸缓释片 + 反相高效液相色谱法　；参考：《湖南师范大学》2014年硕士论文

【摘要】：目的：月经过多严重影响患者健康及正常生活,可致缺铁性贫血和生活质量下降,常见治疗方法有手术和药物治疗。氨甲环酸是一种抗纤维蛋白溶解剂,临床上已经证明其能有效治疗月经过多。本课题采用亲水性骨架缓释材料羟丙甲纤维素,研制开发出一种高效、低毒、稳定、依从性好的治疗月经过多的3.1类新药氨甲环酸缓释片,研究与完善其处方工艺、质量标准、稳定性等临床前工作,整理与总结临床前申报所需的全部试验资料和文献资料,提出新药和医院新制剂临床前注册申请,获得新药和医院新制剂临床批件,填补国内空缺,降低医疗费用,方便临床应用,有望成为治疗月经过多的首选药物,社会与经济意义重大。方法：根据已有的文献资料的基础上,本课题制订氨甲环酸缓释片的制备和工艺,并对其进行优化。采用反相高相液相色谱法。色谱柱Diamonsil C18；流动相0.23%十二烷基硫酸钠溶液-甲醇(60：40,V/V)；检测波长220nm；流速0.8mLmin-1温30℃；进样量20μL。确定色谱条件并对其进行方法学验证,确定所建立方法的可行性与可靠性。 1制剂处方工艺：进行处方前研究,以体外释放度为主要考察指标,从处方因素和工艺因素等方面详细考察各种因素对药物释放行为的影响,根据研究结果确定其最佳处方和工艺。 2质量研究与标准制定：对药品的性状、鉴别、检查、含量测定等进行研究,建立释放度、微生物限度、有关物质和含量测定等的方法学,制定完善、可行、可控的质量标准。 3制剂稳定性研究：对氨甲环酸缓释片进行稳定性影响因素试验、加速试验、长期试验,以性状、释放度、有关物质、含量、微生物限度等为重点检查项目,考察温度、湿度、光照对其质量的影响,以便确定其有效期。结论：1选择HPMC为亲水凝胶缓释骨架,筛选出最佳处方：氨甲环酸650mg；微晶纤维素28mg；微粉硅胶2g；预交化淀粉31mg；羟丙甲纤维素(K4)155g；聚维酮(K30)53mg；硬脂酸20mg；硬脂酸镁11mg。采用湿法制粒压片,硬度18～20kg,片重为950mg。 2采用《中国药典》2010年版附录XD第二法,以水、0.1mol L-1盐酸、pH4.5醋酸盐缓冲液和pH6.8磷酸盐缓冲液为释放介质,体积 900mL,采用RP-HPLC法对氨甲环酸缓释片在不同释放介质中的释放度研究。初步确定本品15～30min释放40～50%,45～90min释放90%,120～150min释放98～100%。证明氨甲环酸缓释片可在规定时间内释放量达到要求。 3制剂中辅料不影响氨甲环酸缓释片的含量测定。氨甲环酸缓释片在0.5007～4.0056mg mL-1范围内峰面积与浓度呈良好的线性关系(r=0.9999)；检测限和定量限分别为1.024、3.413gg；平均回收率均在98～102%(RSD%≤2%,n=9)。 4稳定性试验结果表明：本品影响因素试验10d、加速试验6个月、长期试验9个月的各项考察指标与0d比较均无明显变化,均在合格范围内,其稳定性良好,有效期暂定2年。 5经检验自制氨甲环酸缓释片的各项指标与进口氨甲环酸缓释片相近。本课题通过建立反相高效液相色谱法测定,对氨甲环酸缓释片进行释放度考察,并对其建立质量标准,结果表明该法准确、简便、快速,可用来对氨甲环酸缓释片进行质量控制。
[Abstract]:Objective: menorrhagia seriously affects the healthy and normal life of the patients, which can lead to iron deficiency anemia and the decline of the quality of life. The common treatment methods are surgical and drug treatment. Methicinic acid is an anti fibrinolytic agent. It has been proved to be effective in the treatment of menorrhagia. It has developed and developed a highly effective, low toxic, stable and compliant 3.1 new drug for the treatment of menorrhagia, methicate sustained release tablets, study and improve the pre clinical work of the prescription, quality standards, stability and so on, to sort out all the test data and documents needed for the pre clinical declaration, and put forward new drugs and hospital new preparations. It is expected to become the first choice for the treatment of menorrhagia, and it is of great social and economic significance to apply for new drugs and new pharmaceutical preparations in hospital, to fill in the domestic vacancies, to reduce the cost of medical treatment and to facilitate the clinical application.
Methods: on the basis of the existing literature, the preparation and process of the slow-release tablets of methicylcyclic acid were prepared and optimized. The reversed phase high phase liquid chromatography, Diamonsil C18, 0.23% liquid phase twelve alkyl sulfate solution methanol (60:40, V/V), detection wavelength 220nm, flow velocity 0.8mLmin-1 temperature 30; A sample size of 20 UF L. was used to determine the chromatographic conditions and verify the method, and determine the feasibility and reliability of the established method.
1 preparation process: pre - prescription study, in vitro release degree as the main index, the effect of various factors on drug release behavior were investigated in detail from prescription factors and technological factors, and the best prescription and technology were determined according to the research results.
2 quality research and standard formulation: Research on drug properties, identification, inspection, content determination, etc., establish the methodology of release degree, microbial limit, related substance and content determination, and establish a perfect, feasible and controllable quality standard.
The stability study of 3 preparations: the stability influence factor test on methicyclic acid sustained-release tablet, the accelerated test, the long-term test, the key examination items with the character, the release degree, the related substance, the content, the microbial limit and so on, to examine the effect of temperature, humidity and light on its quality, in order to determine its validity.
Conclusion: 1 select HPMC as the sustained-release skeleton of hydrophilic gel, and select the best prescription: methicyl acid 650mg, microcrystalline cellulose 28mg, micropowder silica gel 2G, preformed starch 31mg, K4 155g, polyvidone (K30) 53mg, stearic acid 20mg, magnesium stearate 11mg. with wet granulation, hardness 18 ~ 20kg, tablet weight as
2 adopt the appendix XD second method of the Chinese Pharmacopoeia >2010 edition, with water, 0.1mol L-1 hydrochloric acid, pH4.5 acetate buffer and pH6.8 phosphate buffer as release medium.
900mL, the release of methicyclic acid sustained-release tablets in different release media was studied by RP-HPLC method. It was preliminarily determined that the release of this product from 15 to 30min was 40 to 50%, 45 to 90min release 90%, and 98 to 100%. released from 120 to 150min to prove that the release amount of methicinic acid could be released in the prescribed time.
The excipients in the 3 preparation did not affect the content determination of methicyclic acid sustained-release tablets. The peak area and concentration of methicyclic acid sustained-release tablets in the range of 0.5007 ~ 4.0056mg mL-1 showed a good linear relationship (r=0.9999), the detection limit and the quantitative limit were 1.024,3.413gg, and the average recovery was 98 to 102% (RSD% < 2%, n=9).
4 the results of the stability test showed that the influence factor test of this product was 10d, the accelerated test was 6 months, and the inspection indexes of the long-term test for 9 months had no obvious changes compared with the 0d. All of them were within the qualified range, and their stability was good and the period of validity was tentatively fixed for 2 years.
5 the indexes of sustained release tablets of homemade tranexamic acid were similar to those of imported tranexamic acid sustained-release tablets.
By establishing a reversed phase high performance liquid chromatography (RP HPLC), the release degree of methicyclic acid sustained-release tablets was investigated and the quality standard was established. The results show that the method is accurate, simple and rapid, and can be used to control the quality of methicyclic acid sustained-release tablets.
【学位授予单位】：湖南师范大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R943

【参考文献】