發(fā)布時(shí)間：2018-11-18 14:53

【摘要】： 本文以MCC為材料,考察了離心法制備微丸過(guò)程中處方工藝因素對(duì)微丸性能的影響,并以二甲雙胍為模型藥物,通過(guò)溶液層積法和粉末層積法對(duì)微丸進(jìn)行了上藥操作,最后嘗試制備了骨架緩釋丸。 對(duì)現(xiàn)有的輔料進(jìn)行分類(lèi),歸納,選取有代表性的幾種進(jìn)行離心造粒,考察其離心造粒時(shí)的成丸特點(diǎn),篩選出最佳輔料,結(jié)果表明,離心法制備微丸時(shí),MCC的成丸性最好。以微丸的收率,圓整度,粒度分布為評(píng)價(jià)指標(biāo),考察起母造粒時(shí)轉(zhuǎn)盤(pán)轉(zhuǎn)速,鼓風(fēng)流量,供液速度,噴氣壓力,制粒溫度等工藝參數(shù)對(duì)微丸性能的影響,通過(guò)星點(diǎn)設(shè)計(jì)效應(yīng)面優(yōu)化工藝參數(shù),考察各參數(shù)之間的相互作用。結(jié)果表明,MCC離心制備微丸時(shí)輔料和粘合劑的用量應(yīng)保持1：1.2-1：1.4的比例,微丸的粒徑范圍在60～10目之間。供液量和供液速度對(duì)微丸的粒徑和粒度分布影響最為顯著,且二者對(duì)微丸的粒徑分布具有交叉影響,供液量一定時(shí),供液速度越大,粒徑越大,粒度分布越寬。轉(zhuǎn)盤(pán)轉(zhuǎn)速和鼓風(fēng)流量對(duì)微丸的成型影響不大,但對(duì)微丸收率有一定的影響,鼓風(fēng)機(jī)轉(zhuǎn)速為28Hz微丸的收率最大。在大量實(shí)驗(yàn)的基礎(chǔ)上編制了微丸制備參數(shù)量化表。 選取小分子水溶性的二甲雙胍為模型藥物,對(duì)制備的MCC素丸進(jìn)行了分別進(jìn)行了溶液層積上藥和粉末層積上藥。通過(guò)單因素和正交試驗(yàn),考察了溶液上藥過(guò)程中工藝參數(shù)對(duì)上藥效率的影響。結(jié)果顯示,以2%HPMC E30溶液為上藥溶液能明顯提高微丸上藥效率并上藥后微丸表面光滑,正交實(shí)驗(yàn)確定上藥最佳工藝條件為：供液速度選為8ml·min-1,上藥溫度為55℃,霧化壓力為0.6Bar,溶液層積上藥效率能可達(dá)到85%以上。同時(shí)通過(guò)單因素試驗(yàn)考察了粉末層積上藥工藝參數(shù)的對(duì)含藥微丸的影響,發(fā)現(xiàn)供粉輔料主藥含量對(duì)微丸的收率具有一定影響,MCC比例越高,微丸的制備效果越好,收率越高,但載藥量降低。在微丸尺寸放大過(guò)程中,供漿速度和供粉速度應(yīng)保持一定的比例,以使藥粉混合物均勻穩(wěn)定的層積到母核上。通過(guò)均勻設(shè)計(jì)實(shí)驗(yàn),得到二者之間的線性關(guān)系,由于本實(shí)驗(yàn)所用的裝置供粉速度一般在30～90g·min-1,故供液速度一般選用60～160ml·min-1之間。比較兩種不同的上藥方式,發(fā)現(xiàn),溶液上藥適用于小劑量的藥物,粉末層積適用于大劑量藥物微丸的制備,含量測(cè)定結(jié)果顯示,二者含量均勻度均滿(mǎn)足藥典的規(guī)定。 在前面實(shí)驗(yàn)的基礎(chǔ)上,以40～60目MCC素丸為母核,通過(guò)粉末層積工藝制備骨架緩釋丸。實(shí)驗(yàn)中發(fā)現(xiàn)HPMC為離心法制備骨架丸的理想材料,不同類(lèi)型的HPMC,骨架丸的釋放性能不同,其中HPMC K15M制備的骨架緩釋丸釋放性能最佳,其用量45%時(shí),骨架丸的體外釋藥穩(wěn)定,無(wú)突釋效應(yīng),12h藥物釋放90%,體外釋放度擬合結(jié)果顯示,該骨架丸的體外釋放速度符合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，

本文編號(hào)：2340347