The effect of granule microstructure on dissolution rate
The effect of granule microstructure on dissolution rate
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DOI：
10.1016/j.powtec.2006.12.012
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发表时间：
2008-02-06
影响因子：
5.2
通讯作者：
Stepanek, Frantisek
中科院分区：
文献类型：
--
作者：
Ansari, Mansoor A.;Stepanek, Frantisek
研究了颗粒微观结构与溶出速率的关系。已通过顶喷流化床造粒制备由甘露醇初级颗粒和PVP水性粘合剂组成的颗粒，并通过原位熔融流化床造粒制备由蔗糖初级颗粒和PEG粘合剂组成的颗粒。颗粒微观结构已系统地通过操纵初级粒度分布和粘合剂含量在每种情况下变化。在这两种情况下，发现颗粒孔隙率是粘合剂含量的递减函数，并且已经观察到孔隙率作为细/粗初级颗粒混合比的函数的最小值，与理论预期一致。用X射线计算机微断层摄影术分析了颗粒的微观结构，并与计算机模拟团聚过程产生的三维“虚拟颗粒”进行了比较。然后测量颗粒的溶出速率。虽然发现孔隙率对甘露醇颗粒的溶出速率有很强的影响，但在蔗糖颗粒的情况下，发现溶出速率实际上与孔隙率无关。在这项工作的过程中建立的配方微结构和微结构溶解的相关性是符合以前的计算机模拟结果，并形成一个计算机辅助颗粒设计方法的一部分。(c)2006 Elsevier B. V.保留所有权利。
The relationship between the microstructure of granules and their dissolution rate has been investigated. Granules consisting of mannitol primary particles and PVP aqueous binder have been prepared by top-spray fluid-bed granulation, and granules consisting of sucrose primary particles and PEG binder by in-situ melt fluid-bed granulation. Granule microstructure has been systematically varied by manipulating the primary particle size distribution and the binder content in each case. In both cases granule porosity was found to be a decreasing function of binder content and a minimum of porosity as function of the fine/coarse primary particle mixing ratio has been observed, in line with theoretical expectations. Granule microstructures have been analysed using X-ray computed micro-tomography and compared with three-dimensional "virtual granules" generated by a computer simulation of the agglomeration process. The dissolution rate of granules has then been measured. While porosity was found to have a strong effect on the dissolution rate of mannitol granules, the dissolution rate was found to be practically independent of porosity in the case of sucrose granules. The formulation-microstructure and microstructure-dissolution correlations established in course of this work are in line with previous computer simulation results and form part of a computer-aided granule design methodology. (c) 2006 Elsevier B.V. All rights reserved.