离心法制备微丸工艺参数的量化控制
发布时间：2018-11-18 14:53
【摘要】： 本文以MCC为材料,考察了离心法制备微丸过程中处方工艺因素对微丸性能的影响,并以二甲双胍为模型药物,通过溶液层积法和粉末层积法对微丸进行了上药操作,最后尝试制备了骨架缓释丸。 对现有的辅料进行分类,归纳,选取有代表性的几种进行离心造粒,考察其离心造粒时的成丸特点,筛选出最佳辅料,结果表明,离心法制备微丸时,MCC的成丸性最好。以微丸的收率,圆整度,粒度分布为评价指标,考察起母造粒时转盘转速,鼓风流量,供液速度,喷气压力,制粒温度等工艺参数对微丸性能的影响,通过星点设计效应面优化工艺参数,考察各参数之间的相互作用。结果表明,MCC离心制备微丸时辅料和粘合剂的用量应保持1：1.2-1：1.4的比例,微丸的粒径范围在60～10目之间。供液量和供液速度对微丸的粒径和粒度分布影响最为显著,且二者对微丸的粒径分布具有交叉影响,供液量一定时,供液速度越大,粒径越大,粒度分布越宽。转盘转速和鼓风流量对微丸的成型影响不大,但对微丸收率有一定的影响,鼓风机转速为28Hz微丸的收率最大。在大量实验的基础上编制了微丸制备参数量化表。 选取小分子水溶性的二甲双胍为模型药物,对制备的MCC素丸进行了分别进行了溶液层积上药和粉末层积上药。通过单因素和正交试验,考察了溶液上药过程中工艺参数对上药效率的影响。结果显示,以2%HPMC E30溶液为上药溶液能明显提高微丸上药效率并上药后微丸表面光滑,正交实验确定上药最佳工艺条件为：供液速度选为8ml·min-1,上药温度为55℃,雾化压力为0.6Bar,溶液层积上药效率能可达到85%以上。同时通过单因素试验考察了粉末层积上药工艺参数的对含药微丸的影响,发现供粉辅料主药含量对微丸的收率具有一定影响,MCC比例越高,微丸的制备效果越好,收率越高,但载药量降低。在微丸尺寸放大过程中,供浆速度和供粉速度应保持一定的比例,以使药粉混合物均匀稳定的层积到母核上。通过均匀设计实验,得到二者之间的线性关系,由于本实验所用的装置供粉速度一般在30～90g·min-1,故供液速度一般选用60～160ml·min-1之间。比较两种不同的上药方式,发现,溶液上药适用于小剂量的药物,粉末层积适用于大剂量药物微丸的制备,含量测定结果显示,二者含量均匀度均满足药典的规定。 在前面实验的基础上,以40～60目MCC素丸为母核,通过粉末层积工艺制备骨架缓释丸。实验中发现HPMC为离心法制备骨架丸的理想材料,不同类型的HPMC,骨架丸的释放性能不同,其中HPMC K15M制备的骨架缓释丸释放性能最佳,其用量45%时,骨架丸的体外释药稳定,无突释效应,12h药物释放90%,体外释放度拟合结果显示,该骨架丸的体外释放速度符合Higuchi方程。
[Abstract]:In this paper, the effects of prescription factors on the properties of pellets in the preparation of pellets by centrifugation were investigated by using MCC as the material, and metformin was used as the model drug. The pellets were treated by solution stratification and powder stratification. Finally, skeleton sustained release pills were prepared. The existing excipients were classified and summarized. Several representative kinds of pellets were selected for centrifugal granulation. The characteristics of pellet formation during centrifugal granulation were investigated and the best excipients were screened. The results showed that the pelletizing property of MCC was the best when the pellets were prepared by centrifugal method. Taking the yield, roundness and particle size distribution of pellets as evaluation indexes, the effects of rotating speed, blast flow rate, liquid supply speed, jet pressure and granulation temperature on the performance of pellets were investigated. The interaction between these parameters was investigated by optimizing the process parameters of star design effect surface. The results showed that the dosage of excipients and binders should be kept at 1: 1.2-1: 1.4 when MCC centrifugation was used to prepare pellets, and the particle size of pellets should be in the range of 6010 mesh. The effect of liquid supply and liquid velocity on the particle size and particle size distribution of the pellets was most significant, and they had a cross effect on the particle size distribution of the pellets. The larger the liquid supply rate was, the larger the particle size was and the wider the particle size distribution was. The rotary speed and blast flow rate had little effect on the pellet forming, but had a certain effect on the pellet yield. The blower speed was the largest yield of 28Hz pellet. On the basis of a large number of experiments, a quantitative table of the preparation parameters of pellets was developed. Metformin, which is water-soluble with small molecules, was selected as the model drug. The MCC pellets were prepared by solution stratification and powder stratification respectively. The effect of process parameters on the application efficiency was investigated by single factor and orthogonal test. The results showed that 2%HPMC E30 solution could obviously improve the drug application efficiency of pellets and the surface of pellets was smooth after the application. The optimum process conditions were determined by orthogonal experiment as follows: the feeding rate was chosen as the application temperature of 8ml min-1, at 55 鈩，
本文编号：2340347
[Abstract]:In this paper, the effects of prescription factors on the properties of pellets in the preparation of pellets by centrifugation were investigated by using MCC as the material, and metformin was used as the model drug. The pellets were treated by solution stratification and powder stratification. Finally, skeleton sustained release pills were prepared. The existing excipients were classified and summarized. Several representative kinds of pellets were selected for centrifugal granulation. The characteristics of pellet formation during centrifugal granulation were investigated and the best excipients were screened. The results showed that the pelletizing property of MCC was the best when the pellets were prepared by centrifugal method. Taking the yield, roundness and particle size distribution of pellets as evaluation indexes, the effects of rotating speed, blast flow rate, liquid supply speed, jet pressure and granulation temperature on the performance of pellets were investigated. The interaction between these parameters was investigated by optimizing the process parameters of star design effect surface. The results showed that the dosage of excipients and binders should be kept at 1: 1.2-1: 1.4 when MCC centrifugation was used to prepare pellets, and the particle size of pellets should be in the range of 6010 mesh. The effect of liquid supply and liquid velocity on the particle size and particle size distribution of the pellets was most significant, and they had a cross effect on the particle size distribution of the pellets. The larger the liquid supply rate was, the larger the particle size was and the wider the particle size distribution was. The rotary speed and blast flow rate had little effect on the pellet forming, but had a certain effect on the pellet yield. The blower speed was the largest yield of 28Hz pellet. On the basis of a large number of experiments, a quantitative table of the preparation parameters of pellets was developed. Metformin, which is water-soluble with small molecules, was selected as the model drug. The MCC pellets were prepared by solution stratification and powder stratification respectively. The effect of process parameters on the application efficiency was investigated by single factor and orthogonal test. The results showed that 2%HPMC E30 solution could obviously improve the drug application efficiency of pellets and the surface of pellets was smooth after the application. The optimum process conditions were determined by orthogonal experiment as follows: the feeding rate was chosen as the application temperature of 8ml min-1, at 55 鈩，
本文编号：2340347
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