Stepanek Frantisek, Loo Adeline, Lim Tiong Shing
Department of Chemical Engineering, Imperial College London, South Kensington Campus, London SW7 2AZ, United Kingdom.
J Pharm Sci. 2006 Jul;95(7):1614-25. doi: 10.1002/jps.20624.
Computational methodology for virtual tablet prototyping has been developed. The methodology consists of two steps: construction of virtual particle compacts of varying composition using the discrete element method (DEM), and the simulation of their dissolution by eroding individual components from the tablet microstructure according to their intrinsic dissolution rates, using the volume-of-fluid (VOF) method. The effective erosion rate obtained from simulations at the particle assembly length-scale is used for the calculation of dissolution time at the tablet length-scale. The methodology is demonstrated on the case of a simple effervescent formulation consisting of sodium bicarbonate-acetic acid effervescent system, sodium chloride as a model active substance, and lactose filler. The experimentally measured dependence of tablet dissolution time on composition and compaction force was found to be in very good agreement with outputs from computer simulations.
已开发出用于虚拟片剂原型制作的计算方法。该方法包括两个步骤：使用离散元法（DEM）构建不同组成的虚拟颗粒压片，以及通过根据各成分的固有溶解速率从片剂微观结构中侵蚀单个成分，使用流体体积（VOF）法模拟其溶解过程。在颗粒组装长度尺度上通过模拟获得的有效侵蚀速率用于计算片剂长度尺度上的溶解时间。该方法在一个简单泡腾制剂的案例中得到了验证，该制剂由碳酸氢钠 - 乙酸泡腾体系、作为模型活性物质的氯化钠和乳糖填充剂组成。实验测得的片剂溶解时间对组成和压实力的依赖性与计算机模拟的结果非常吻合。
