Technical Services/Manufacturing Science Division, Eli Lilly & Company, Indianapolis, IN, 46285, USA.
King's College London, Institute of Pharmaceutical Science, London, SE1 9NH, UK.
Int J Pharm. 2016 Oct 15;512(1):224-233. doi: 10.1016/j.ijpharm.2016.08.050. Epub 2016 Aug 26.
The feasibility of a novel reverse-phase wet granulation process has been established and potential advantages identified. Granule growth in the reverse-phase process proceeds via a steady state growth mechanism controlled by capillary forces, whereas granule growth in the conventional process proceeds via an induction growth regime controlled by viscous forces. The resultant reverse-phase granules generally have greater mass mean diameter and lower intragranular porosity when compared to conventional granules prepared under the same liquid saturation and impeller speed conditions indicating the two processes may be operating under different growth regimes. Given the observed differences in growth mechanism and consolidation behaviour of the reverse-phase and conventional granules the applicability of the current conventional granulation regime map is unclear. The aim of the present study was therefore to construct and evaluate a growth regime map, which depicts the regime as a function of liquid saturation and Stokes deformation number, for the reverse-phase granulation process. Stokes deformation number was shown to be a good predictor of both granule mass mean diameter and intragranular porosity over a wide range of process conditions. The data presented support the hypothesis that reverse-phase granules have a greater amount of surface liquid present which can dissipate collision energy and resist granule rebound resulting in the greater granule growth observed. As a result the reverse-phase granulation process results in a greater degree of granule consolidation than that produced using the conventional granulation process. Stokes deformation number was capable of differentiating these differences in the granulation process.
已经确定了新型反相湿法造粒工艺的可行性,并确定了潜在的优势。反相工艺中的颗粒生长通过由毛细力控制的稳态生长机制进行,而常规工艺中的颗粒生长通过由粘性力控制的感应生长机制进行。与在相同的液体饱和度和叶轮速度条件下制备的常规颗粒相比,所得反相颗粒通常具有更大的质量平均直径和更低的颗粒内孔隙率,这表明这两个过程可能在不同的生长机制下运行。鉴于观察到反相和常规颗粒的生长机制和固结行为存在差异,当前常规造粒区图的适用性尚不清楚。因此,本研究的目的是构建和评估一个生长区图,该图将该区域描绘为液体饱和度和斯托克斯变形数的函数,用于反相造粒过程。斯托克斯变形数被证明是在广泛的工艺条件下预测颗粒质量平均直径和颗粒内孔隙率的良好指标。所提出的数据支持了这样一种假设,即反相颗粒具有更多的表面液体,这些液体可以耗散碰撞能量并抵抗颗粒反弹,从而导致观察到的更大颗粒生长。因此,反相造粒工艺导致颗粒固结程度大于使用常规造粒工艺产生的程度。斯托克斯变形数能够区分造粒过程中的这些差异。