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

Maria Adobes-Vidal, Faduma M. Maddar, Dmitry Momotenko, Leslie P. Hughes, Stephen A.C. Wren, Laura N. Poloni, Michael D. Ward, Patrick R. Unwin

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)4421-4429
Number of pages9
JournalCrystal Growth and Design
Volume16
Issue number8
DOIs
StatePublished - Aug 3 2016

ASJC Scopus subject areas

  • Chemistry(all)
  • Materials Science(all)
  • Condensed Matter Physics

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    Adobes-Vidal, M., Maddar, F. M., Momotenko, D., Hughes, L. P., Wren, S. A. C., Poloni, L. N., Ward, M. D., & Unwin, P. R. (2016). Face-Discriminating Dissolution Kinetics of Furosemide Single Crystals: In Situ Three-Dimensional Multi-Microscopy and Modeling. Crystal Growth and Design, 16(8), 4421-4429. https://doi.org/10.1021/acs.cgd.6b00543