TY-202片的制备及质量研究

发布时间：2018-03-01 10:46

本文关键词： 肺动脉高压制备工艺质量标准稳定性研究　出处：《河南大学》2014年硕士论文　论文类型：学位论文

【摘要】：肺动脉高压作为目前临床非常见的疾病之一,具有较高的致死率和致残率,其临床诊治一直是医学界的重要难题。临床研究证实,肺动脉高压的发病与血管收缩、原位血栓的形成等有着密切的关系,降低患者的心脏负荷和改善其血运情况是治疗肺动脉高压的重要途径。随着临床研究的不断深入,内皮素受体拮抗剂在治疗肺动脉高压方面的临床疗效备受关注。TY-202作为血管内皮素拮抗剂,可通过抑制ETA受体和ETB受体发挥较为明显的抗肺血管收缩和抑制血管重构的临床效果。TY-202的各类制剂已获FDA批准在美国及周边国家上市,其临床效果颇受肯定。因此,开发以TY-202为活性成分的药物制剂对于缓解肺动脉高压临床用药缺乏及降低肺动脉高压患者医疗经济成本具有重要的意义。通过对TY-202溶解性、油水分配系数、熔点等理化性质进行考察,归属其为BCS二类药物。建立体外溶出度评价方法,照溶出度测定法(中国药典二部附录XC,第二法)优先以pH5.0醋酸缓冲液900ml为溶剂,转速50转/分,于220nm的波长处检测,以HPLC法计算每片溶出量,并与国外市售品进行对比,评价原研一致性。处方工艺主要包括片剂制备以及包衣操作。通过正交试验,以片重差异、溶出度、硬度为综合指标,筛选最佳处方,并进行优化,确定最终素片处方,并对片剂进行包衣工艺研究,以包衣效率为考察指标正交试验优化包衣参数,以确定的片剂处方及包衣参数进行中试三批样品生产。通过建立高效液相色谱法,对TY-202片剂质量进行研究,测定有关物质、含量和溶出度,并对三批中试样品进行加速试验,在6个月内TY-202片的外观、含量、溶出度未出现明显差异,有关物质随放置时间有不同程度的变化,但均符合规定；以市售包装样品长期稳定性试验9个月各项指标均未发生明显变化,均在质量控制范围内。
[Abstract]:Pulmonary hypertension, as one of the most common diseases, has a high mortality and disability rate. The clinical diagnosis and treatment of pulmonary hypertension has been an important problem in the medical field. Clinical studies have confirmed that the pathogenesis of pulmonary hypertension and vasoconstriction. There is a close relationship between the formation of in situ thrombosis and so on. It is an important way to treat pulmonary hypertension to reduce the cardiac load and improve the blood flow of the patients. The clinical efficacy of endothelin receptor antagonist in the treatment of pulmonary hypertension has attracted much attention. TY-202 is used as endothelin antagonist. The clinical effects of anti-pulmonary vasoconstriction and vascular remodeling by inhibiting ETA receptor and ETB receptor .TY-202 have been approved by FDA to be listed in the United States and neighboring countries. The development of drug preparation with TY-202 as the active component is of great significance in alleviating the shortage of pulmonary hypertension and reducing the medical cost of patients with pulmonary hypertension. The solubility of TY-202, oil / water partition coefficient, melting point and other physicochemical properties were investigated. The method of dissolution evaluation in vitro was established. PH5.0 acetic acid buffer (900ml) was used as solvent in the second appendix of Chinese Pharmacopoeia, and was detected at 220 nm wavelength. The dissolution of each tablet was calculated by HPLC method, and compared with that of foreign market. To evaluate the consistency of original research. The prescription process mainly includes tablet preparation and coating operation. Through orthogonal test, the optimum prescription was screened and optimized to determine the final prescription by taking the weight difference of tablets, dissolution and hardness as the comprehensive index. The coating process of tablets was studied and the coating parameters were optimized by orthogonal test with coating efficiency as the index. The tablet formulation and coating parameters were produced in the pilot-scale three batches of samples. The quality of TY-202 tablets was studied by high performance liquid chromatography (HPLC). The related substances, contents and dissolution were determined, and accelerated tests were carried out on three pilot-scale samples. The appearance and content of TY-202 tablets were determined within 6 months. There was no significant difference in dissolution, the relative substances varied with the time of storage, but all of them were in accordance with the regulations, and the indexes of the long-term stability test of the package samples on the market for 9 months did not change obviously, all of them were within the range of quality control.
【学位授予单位】：河南大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R943

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