Mechanisms of drug release from a melt-milled, poorly soluble drug substance.

IF 3.7 3区 医学 Q2 CHEMISTRY, MEDICINAL
Dominik Sleziona, David R Ely, Markus Thommes
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引用次数: 0

Abstract

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.

熔融研磨的难溶性药物释放机制
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,其中应考虑到两种主要的溶解机制:表面反应和扩散。一种很有前途的工具就是所谓的固体晶体悬浮液,一种由纯晶体物质组成的固体分散体。在这一概念中,减小药物颗粒大小并将颗粒嵌入亲水性赋形剂中可提高溶解动力学。因此,通过改良的搅拌介质研磨工艺生产出了含有亚微米药物颗粒的固体晶体悬浮液。几何相场法被用来模拟药物颗粒的溶解行为。在珠磨机中研磨载体材料木糖醇和模型药物格列齐特。对产品的体外溶解曲线进行建模,以深入了解溶解过程的物理特性。所使用的数值工具有望成为预测新开发制剂溶出行为的重要方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
7.30
自引率
13.20%
发文量
367
审稿时长
33 days
期刊介绍: The Journal of Pharmaceutical Sciences will publish original research papers, original research notes, invited topical reviews (including Minireviews), and editorial commentary and news. The area of focus shall be concepts in basic pharmaceutical science and such topics as chemical processing of pharmaceuticals, including crystallization, lyophilization, chemical stability of drugs, pharmacokinetics, biopharmaceutics, pharmacodynamics, pro-drug developments, metabolic disposition of bioactive agents, dosage form design, protein-peptide chemistry and biotechnology specifically as these relate to pharmaceutical technology, and targeted drug delivery.
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