Face-Discriminating Dissolution Kinetics of Furosemide Single Crystals: In Situ Three-Dimensional Multi-Microscopy and Modeling

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• 作者：Maria Adobes-Vidal ; Faduma M. Maddar ; Dmitry Momotenko ; Leslie P. Hughes ; Stephen A. C. Wren ; Laura N. Poloni ; Michael D. Ward ; Patrick R. Unwin
• 刊名：Crystal Growth & Design
• 出版年：2016
• 出版时间：August 3, 2016
• 年：2016
• 卷：16
• 期：8
• 页码：4421-4429
• 全文大小：550K
• 年卷期：0
• ISSN：1528-7505

文摘

A versatile in situ multi-microscopy approach to study the dissolution kinetics of single crystals is described, using the loop diuretic drug furosemide as a testbed to demonstrate the utility of the approach. Using optical microscopy and scanning ion-conductance microscopy in combination, the dissolution rate of individual crystallographically independent crystal faces can be measured quantitatively while providing a direct visualization of the evolution of crystal morphology in real time in three dimensions. Finite element method models using experimental data enables quantitative analysis of dissolution fluxes for individual faces and determination of the limiting process—mass transport or interfacial kinetics—that regulates dissolution. A key feature of the approach is that isolated crystals (typically <60 μm largest characteristic dimension) in solution during dissolution experience high and well-defined diffusion rates. The ability to obtain this quantitative information for individual crystal faces suggests a pathway to understanding crystal dissolution at the molecular level and regulating bioavailability, for example, through manipulation of crystal morphology.