【作者】 王晓君；

【导师】 高子彬；

【作者基本信息】 河北科技大学 ， 药物化学， 2014， 硕士

【摘要】 精神分裂症是精神疾病中患病率最高的一种疾病，病程慢性进行性且具有复发倾向。寻找安全、有效的抗精神病药物是一项巨大的挑战，目前，抗精神病药物的研发焦点集中在非典型抗精神病药物上。伊潘立酮是一种非典型抗精神病药物，是5-羟色胺-2（5-HT2）和多巴胺2（D2）受体阻滞药。伊潘立酮于2009年5月6日获得美国FDA批准上市，用于治疗精神分裂症。目前，国内尚未批准上市。本课题的难点在于伊潘立酮为难溶性药物（BCS Ⅱ类），能否制备与原研产品具有相似的溶出行为、可工业化生产的伊潘立酮片剂是本课题的关键。本课题对伊潘立酮片的制备及其质量控制进行了研究，为伊潘立酮片进行工业化生产提供实验依据。首先对伊潘立酮片的处方和工艺进行了筛选。根据上市品在4种溶出介质中的溶出曲线，本课题中选用0.1mol·L-1盐酸、15min时的溶出度为指标对处方及工艺进行了筛选。结果显示：最终确立的处方及球磨机粉碎工艺制备的伊潘立酮片与上市品相比，溶出曲线相似。为控制伊潘立酮片的质量，建立了紫外分光光度含量测定法和溶出度检查方法。根据小试生产中的处方和工艺参数制备了3批产品，用于稳定性研究。影响因素试验、加速试验和长期试验的结果显示：该制剂含量、含量均匀度、溶出度和有关物质等指标在试验过程无明显变化，说明该制剂稳定性良好。本课题确定了伊潘立酮片的处方及其中试生产工艺参数，为进一步实现工业化生产提供了依据。更多还原

【Abstract】 Schizophrenia is a disease with the highest incidence of mental illness, which haschronic progressive course and has the tendency to relapse. It is a huge challenge to lookfor the safe and effective antipsychotic drugs. The focus of antipsychotic drugs is theatypical antipsychotics in the current researches. Iloperidone, an atypical antipsychoticdrug that was approved by FDA on May6,2009, is a dual-retardant of5-HT2and D2receptors for treating schizophrenia. Now it has not been approved to produce withinChina. Iloperidone is an insoluble drug. The key of the study is that whether thedissolution behavior of iloperidone tablet we prepared is similar to original product, andwhether the tablets can be produced industrially.This study was focused on the preparation and quality control of the iloperidonetablets, providing the experimental basis for industrialized production of iloperidonetablets. Firstly, according to the dissolution curve of the listed products in the four kinds ofdissolution medium, the formulation and process were screened with the index of thedrug’s dissolution of15min in0.1mol·L-1HCl. Based on the above study, the optimalformulation was determined. These results showed that the dissolution curve ofiloperidone tablets prepared by the optimal formulation was similar with that of the listedproducts.Secondly, the preparation’s quality control was studied via UV spectrometry for thecontent determination and the dissolubility test. According to the prescription andpreparation process parameters of the pilot production, we produced three batches ofproducts that be used to study the stability. These results of the affected factor test,speed-up test and long-term test showed that the preparation indexes, such as content,content uniformity, dissolution and related indicators, were unchanged obviously in thetest process, indicating that the preparation has good stability.In the study, the prescription and pilot production process parameters weredetermined, providing a basis for the industrialized production.更多还原