Sleziona Dominik, Ely David R, Thommes Markus
TU Dortmund, Department of Biochemical and Chemical Engineering, Laboratory of Solids Process Engineering, Emil-Figge-Str. 68, 44227 Dortmund, Germany.
Ivy Tech Community College, 3101 S Creasy Ln, Lafayette, IN 47905, USA.
J Pharm Sci. 2025 Jan;114(1):394-401. doi: 10.1016/j.xphs.2024.10.016. Epub 2024 Oct 18.
Increasing the dissolution kinetics of low aqueous soluble drugs is one of the main priorities in drug formulation. New strategies must be developed, which should consider the two main dissolution mechanisms: surface reaction and diffusion. One promising tool is the so-called solid crystal suspension, a solid dispersion consisting of purely crystalline substances. In this concept, reducing the drug particle size and embedding the particles in a hydrophilic excipient increases the dissolution kinetics. Therefore, a solid crystal suspension containing submicron drug particles was produced via a modified stirred media milling process. A geometrical phase-field approach was used to model the dissolution behavior of the drug particles. A carrier material, xylitol, and the model drug substance, griseofulvin, were ground in a pearl mill. The in-vitro dissolution profile of the product was modeled to gain a deep physical understanding of the dissolution process. The used numerical tool has the potential to be a valuable approach for predicting the dissolution behavior of newly developed formulation strategies.
提高低水溶性药物的溶解动力学是药物制剂的主要优先事项之一。必须开发新的策略，这些策略应考虑两种主要的溶解机制：表面反应和扩散。一种有前景的工具是所谓的固体晶体悬浮液，一种由纯结晶物质组成的固体分散体。在这个概念中，减小药物粒径并将颗粒嵌入亲水性辅料中可提高溶解动力学。因此，通过改进的搅拌介质研磨工艺制备了含有亚微米药物颗粒的固体晶体悬浮液。采用几何相场方法对药物颗粒的溶解行为进行建模。将载体材料木糖醇和模型药物灰黄霉素在珠磨机中研磨。对该产品的体外溶出曲线进行建模，以深入了解溶解过程的物理原理。所使用的数值工具有可能成为预测新开发制剂策略溶解行为的有价值方法。
