两种AngⅡ拮抗剂片剂和ST1213渗透泵控释片的制备

发布时间：2018-01-03 15:31

本文关键词：两种AngⅡ拮抗剂片剂和ST1213渗透泵控释片的制备　出处：《广东药学院》2015年硕士论文　论文类型：学位论文

【摘要】：本课题主要研究两种AngⅡ拮抗片剂即ST0723、ST0903片剂的处方工艺以及ST1213渗透泵控释片的制备。ST0723采用湿法制粒工艺,通过选择粘合剂1,ST0903则采用干法制粒工艺。ST1213渗透泵控释片的制备选用辅料V、辅料VII,ST1213固体分散体作为片芯材料,采用辅料VIII,辅料IX、辅料X作为包衣材料来制备ST1213渗透泵片。本实验主要分以下三个部分。1、ST0723片剂的制备ST0723为血管紧张素Ⅱ(AngiotensinⅡ,AngⅡ)受体抑制剂,为AngⅡ型拮抗片剂,属于难溶性药物。为了提高其溶出度,选择辅料I,辅料V作为填充剂,辅料VI作为崩解剂,辅料IV作为助流剂,辅料III作为润滑剂。实验分别考察了粘合剂的选择,崩解剂的用量,不同压力等对溶出度的影响。通过微调处方,以溶出度为考察指标,以达到与原研药的溶出度相似性。2、ST0903片剂的制备ST0903同样属于血管紧张素Ⅱ(AngiotensinⅡ,AngⅡ)受体抑制剂,为AngⅡ型拮抗片剂,不仅为难溶性药物,而且不稳定,具有一定的引湿性,存在多种晶型。考虑湿法制粒中产生晶型转变和性质变化,采用干法制粒,选择辅料I作为填充剂,辅料II作为崩解剂,辅料IV作为助流剂,辅料III作为润滑剂。实验分别考察了辊轮转速、辊轮压力、崩解剂用量等对溶出度的影响,通过微调处方改变相关参数工艺,来提高溶出度,与原研药进行曲线对比,达到原研药的溶出效果。3、ST1213渗透泵控释片的制备本实验利用紫外分光度法对ST1213渗透泵片的体外释放度进行测定。通过制备ST1213固体分散体达到增溶效果,以星点设计-效应面法优化包衣液处方。片芯材料选用辅料V、辅料VII作为填充剂。包衣液处方选用辅料VIII,辅料IX、辅料X、丙酮:异丙醇为4:1的溶媒作为包衣材料,以12h累计释放度为指标,以不同包衣增重,释药孔径大小,辅料IX用量、增塑剂用量四个因素考察对释放的影响,利用星点设计对ST1213渗透泵控释片处方进行处方优化,根据效应面得到最优处方:包衣增重3.00%,致孔剂用量0.71%,释药孔径大小为0.40mm。制备三批最优处方样品与预测的值进行模型验证,自制渗透泵与预测值相一致,12 h内药物呈零级释放特征,重现性良好。
[Abstract]:This paper mainly studies two kinds of Ang II antagonist tablets ST0723, ST0903 tablet prescription and ST1213 osmotic pump tablets.ST0723 was prepared by the wet granulation method, by choosing 1 ST0903 with.ST1213 adhesive, dry granulation process of osmotic pump tablets were prepared using V materials, VII materials, ST1213 solid dispersion as core materials, the materials VIII, IX accessories, X accessories as coating materials to prepare ST1213 osmotic pump tablets. This experiment is mainly divided into the following three parts.1, ST0723 tablet preparation for ST0723 angiotensin II (Angiotensin II, Ang II) receptor inhibitor, Ang type II antagonist tablets. Belong to the insoluble drug. In order to improve the dissolution rate of I, the choice of materials, accessories and accessories as VI V as a filler, disintegrating agent, IV as glidants accessories, accessories III as lubricant. Experimental investigation of the binder selection, disintegrating agent used Different amount of pressure on the degree of dissolution. By means of adjusting the prescription to dissolution rate as indices to achieve with the original drug dissolution of similar.2, ST0903 in the preparation of tablets ST0903 also belong to angiotensin II (Angiotensin II, Ang II) for type II receptor inhibitor, Ang antagonistic tablets, not only for insoluble drugs, and unstable, with wet properties, there are a variety of crystal type. Considering the changes of crystal transformation and properties of wet granulation, by dry granulation, the choice of materials I as filler materials II as disintegrating agent, IV as glidants accessories, accessories as III lubricant. Experimental investigation of the roller speed, roller pressure, disintegrating agent dosage on the dissolution effect, by means of adjusting the parameters related to prescription change process, to improve the dissolution curve compared with the original drug, reach the dissolution effect of.3 of the original drug, ST1213 osmotic pump controlled release The preparation of this experiment using the ultraviolet spectrophotometry of ST1213 osmotic pump tablets in vitro release were determined. Through the preparation of ST1213 solid dispersion to solubilization effect, with ccd-rsm optimized coating formulation. The core material selection of materials V, VII materials as filler. The coating formulation of selected materials VIII X, IX accessories, accessories, acetone and isopropanol as solvent: 4:1 as coating material, 12h cumulative release rate as the index in different coating weight, release pore size, the amount of IX accessories, plasticizer four factors on the release effect of ST1213 osmotic pump controlled release tablets optimized by central composite design, according to the effect of the optimal prescription: surface coating weight of 3%, the amount of the porogen 0.71% release pore size samples and prepare for the three batch of the optimal prescription of 0.40mm. was predicted value of model validation, osmotic pump and forecast The values were the same. The drug in 12 h was characterized by zero level release, and the reproducibility was good.

【学位授予单位】：广东药学院
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R943

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