Twin screw wet granulation: Influence of formulation parameters on granule properties and growth behavior
Twin screw wet granulation: Influence of formulation parameters on granule properties and growth behavior
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DOI：
10.1016/j.powtec.2012.04.035
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发表时间：
2013-04-01
影响因子：
5.2
通讯作者：
Litster, J. D.
中科院分区：
文献类型：
--
作者：
El Hagrasy, A. S.;Hennenkamp, J. R.;Litster, J. D.
采用16mm双螺杆造粒机，研究了配方参数对颗粒性能和生长行为的影响。采用乳糖（73.5%）、微晶纤维素（20%）、羟丙基甲基纤维素（5%）和交联纤维素钠（1.5%）组成的模型安慰剂配方。通过使用具有独特粒度属性的三种等级的乳糖来实现初级粒度的变化。结合剂在干燥与液体形式也进行了检查。以0.05为间隔，将液固比（L/S）在0.15 ~ 0.45之间变化，研究了不同等级乳糖的成粒和生长行为。双螺杆造粒机对配方特性的显著变化表现出整体稳健性，其中三种配方等级在不同的L/S比下表现出相似的生长行为。然而，粒度分析表明，所有配方等级的双峰分布，即使在最低液面也存在块状和未颗粒状的细粒。这表明造粒机内部的液体分布不佳，特别是以滴注方式添加液体，并且混合不同组分的停留时间相对较短。与在干燥形式中使用粘合剂相比，在液相中添加粘合剂减少了产生细粒的水平。颗粒孔隙度随固相比和粘结剂含量的增加而减小，表明颗粒固结程度增强。本研究的结果强调需要改善液体分布内的双螺杆造粒机，以优化其利用在一个连续的制造环境。(C) 2012 Elsevier B.V.版权所有
This study investigated the effect of formulation parameters on granule properties and growth behavior using a 16 mm twin screw granulator. A model placebo formulation composed of lactose (73.5%), microcrystalline cellulose (20%), hydroxypropylmethyl cellulose (5%) and croscarmellose sodium (1.5%) was used. Variation in the primary particle size was achieved by using three grades of lactose with unique particle size attributes. The incorporation of the binder in a dry versus liquid form was also examined. The granule formation and growth behavior of the different grades of lactose was investigated by varying the liquid to solid (L/S) ratio between 0.15 and 0.45 at 0.05 intervals. The twin screw granulator demonstrated an overall robustness towards remarkable changes in the formulation characteristics, where the three formulation grades displayed similar growth behavior at different L/S ratios. However, granule size analysis demonstrated a bimodal distribution for all formulation grades, with the presence of lumps and un-granulated fines even at the lowest liquid level. This indicated poor liquid distribution inside the granulator, particularly with the liquid addition in a dripping mode and the relatively short residence time available for mixing the different components. The addition of the binder in the liquid phase reduced the level of fines generated in comparison to using binder in the dry form. Granule porosity decreased with the increase in US ratio and percent binder in the liquid phase, indicating more consolidation. The results of this study highlight the need to improve liquid distribution within a twin screw granulator to optimize its utilization in a continuous manufacturing environment. (C) 2012 Elsevier B.V. All rights reserved.