喷雾干燥法制备微囊的处方和工艺参数的量化控制

发布时间：2018-08-06 11:27

【摘要】：微囊化技术是指利用天然或者合成的高分子包囊材料,将固体、液体或气体物质包在微小、半透性或密封的囊内,使内容物在特定条件下以可控的速率进行释放的技术。 本文利用三种理化性质截然不同的模型药物,筛选出各自有针对性的处方和工艺条件,对制备微囊和微球有理论指导意义;实验通过对喷雾干燥制备微囊的介绍和影响因素的探究,找出了影响药物微囊化的因素及解决办法,并将影响因素分为工艺因素和处方因素两方面。处方影响因素包括药物及囊材的选择及浓度、药物与囊材的比例、各种辅料的用量及选择;工艺影响因素包括进料速率、雾化压力、进风温度等。同时本文制定了微囊评价的的质量标准,通过对其评价指标如微囊载药量、包封率、粒径大小、粒径分布、微囊外观、释放度等方面的测定,找出了喷雾干燥制备微囊的最佳工艺条件和最佳处方。并对样品分别进行了稳定性考察,结果表明被检测样品符合质量标准。 在乙醇不溶性药物的喷雾干燥实验中,我们选取二甲双胍作为模型药物,并以此制备二甲双胍缓释微囊。我们经过对单因素考察确定了喷雾干燥法制备二甲双胍微囊的工艺及处方的大致范围,并利用正交试验法确定了最优工艺及处方条件,得到最优参数为:喷雾干燥法制备微囊的最佳处方为囊材用量为5%,芯材比1:3,增塑剂用量为5%,抗粘剂的用量为20%;进风温度145℃,出风温度80℃,喷雾压力0.30Mpa,进料速度10ml/min。经考察,二甲双胍微囊具有良好的缓释效果,且粒径分布均匀,稳定性良好。 在乙醇可溶性药物的喷雾干燥实验中,我们选取具有苦味的罗红霉素作为模型药物制备微囊,并以掩味效果作为新的评价指标之一。我们经过对单因素考察确定了喷雾干燥法制备罗红霉素微囊的工艺及处方的大致范围,并利用正交试验法确定了最优工艺及处方条件:进风温度170℃,出风温度80℃,喷雾压力0.40Mpa,进料速度15ml/min;处方因素:囊材Eudragit L100用量为6%,芯材比1:4,增塑剂用量为5%,抗粘剂的用量为20%。同时,所制得微囊包封率在95%上,同时微囊具有良好的掩味效果。 在液体药物固体化实验中,我们选取的模型药物为维生素A,以提高维生素A的稳定性,使其更便于贮藏和应用。本文主要研究了喷雾干燥法制备维生素A微囊的制备工艺、理化性质和稳定性。我们探究了影响维生素A微囊化的多种因素,如壁材的浓度,芯材的质量,高速剪切转度,并对工艺因素等进行了研究并利用正交试验进行优化,确定最优实验条件如下:进风温度175℃,搅拌时间35min,搅拌速度4800 r/min,雾化压力0.26MPa。囊材用量6%、乳化剂用量2.5%、芯材比0.55:1、油水相比例20%。所得微囊固体化效果良好,稳定性良好。 实验结果表明,对三种不同类型药物利用喷雾干燥法制备微囊,均取得了良好的效果,达到了预期期望。
[Abstract]:Microencapsulation technology refers to the technology of using natural or synthetic polymer encapsulation materials to encapsulate solid, liquid or gaseous substances in tiny, semi-permeable or sealed capsules, so that the contents can be released at a controllable rate under certain conditions. In this paper, three different physicochemical properties of model drugs were used to screen out their respective prescriptions and technological conditions, which have theoretical significance for the preparation of microcapsules and microspheres. Through the introduction of the preparation of microcapsules by spray drying and the study of the influencing factors, the factors affecting the drug microencapsulation and their solutions were found out, and the influencing factors were divided into two aspects: technological factors and prescription factors. The factors influencing prescription include the choice and concentration of medicine and capsule material, the ratio of drug to capsule material, the dosage and selection of various excipients, and the technological factors include feed rate, atomization pressure, inlet air temperature and so on. At the same time, the quality standard of microencapsulation evaluation was established, and the evaluation indexes such as drug loading, encapsulation efficiency, particle size, particle size distribution, appearance and release of microcapsules were determined. The optimum conditions and prescription of spray drying for preparation of microcapsules were found out. The stability of the samples was investigated, and the results showed that the samples met the quality standard. In the spray drying experiment of ethanol insoluble drugs we selected metformin as model drug and prepared metformin sustained-release microcapsules. The preparation process of metformin microcapsules by spray drying method and the general range of its formulation were determined by single factor investigation, and the optimum process and prescription conditions were determined by orthogonal test. The optimum parameters are as follows: the best formulation for the preparation of microcapsules by spray drying method is as follows: the amount of capsule material is 5, the ratio of core to material is 1: 3, the amount of plasticizer is 5 and the amount of anti-viscosity is 20. The inlet temperature is 145 鈩，

本文编号：2167594