Department of Pharmaceutical Biosciences and the Swedish Drug Delivery Center (SweDeliver), Uppsala University, P.O. Box 591, 751 24 Uppsala, Sweden.
Department of Pharmaceutical Biosciences and the Swedish Drug Delivery Center (SweDeliver), Uppsala University, P.O. Box 591, 751 24 Uppsala, Sweden.
Int J Pharm. 2023 Feb 25;633:122626. doi: 10.1016/j.ijpharm.2023.122626. Epub 2023 Jan 20.
A new modelling approach for dissolution of polydisperse powders is developed within the framework of the classical Noyes-Whitney/Nernst-Brunner analysis. Its distinguishing feature is that the underlying continuous particle-size distribution is retained. Two different but related dependencies of the diffusion-layer thickness on particle size are considered. First, a power-law dependence that interpolates between a thickness that is proportional to (or equals) the particle radius (obtained when the exponent equals 1) and a constant thickness (obtained when the exponent is 0). Second, a piecewise linear function such that the thickness equals the particle radius for sufficiently small particles and is constant for larger ones. The modelling approach is exemplified by consideration of a lognormal particle-size distribution. Highly accurate closed-form expressions for the fraction of dissolved drug are obtained for dissolution under sink conditions (which are exact if the diffusion-layer thickness is radius-independent). Moreover, it is demonstrated that any result derived under sink conditions can be reused to determine the fraction of dissolved/absorbed drug under non-sink conditions, using the concept of a retarded time. Comparison with literature data and experiments are used to validate the modelling approach and to demonstrate its usefulness in a practical context.
一种新的多分散粉末溶解建模方法是在经典的 Noyes-Whitney/Nernst-Brunner 分析框架内开发的。其特点是保留了基础的连续粒度分布。考虑了两种不同但相关的扩散层厚度与粒径的依赖关系。首先，幂律关系在与粒径成正比（或等于）的厚度（当指数等于 1 时获得）和恒定厚度（当指数为 0 时获得）之间进行插值。其次，分段线性函数，使得厚度对于足够小的颗粒等于颗粒半径，对于较大的颗粒则为常数。通过考虑对数正态粒度分布来说明建模方法。在溶出度为（如果扩散层厚度与半径无关，则为精确）的情况下，获得了溶解在汇条件下溶解药物分数的高度精确的闭式表达式。此外，还证明了在非汇条件下，任何在汇条件下得出的结果都可以通过使用延迟时间的概念，重新用于确定溶解/吸收药物的分数。与文献数据和实验的比较用于验证建模方法，并展示其在实际情况下的有用性。
