Effect of pH on the Surface Layer of Molecular Crystals at the Solid-Liquid Interface

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Dissolution of solid matter into aqueous solution is one of the most challenging physicochemical aspects related to drug development. While influenced by several parameters, the effect of pH remains the most important one to be fully understood. The dissolution process is essentially controlled by activity at the surface of the molecular crystals, which is difficult to characterize experimentally. To address this, a combination of in situ atomic force microscopy (AFM) with molecular dynamics (MD) simulation is reported. AFM allows for direct visualization of the crystal surface of basic and acidic model compounds (carvedilol and ibuprofen) in contact with an aqueous medium with varying pH. A dramatic increase in surface mobility in the solid-liquid interface could be observed experimentally as a function of pH. The in situ AFM approach opens up for a more detailed understanding of the behavior of particulate matter in solution with importance at different levels, ranging from engineering aspects related to crystallization, and biological considerations related to bioavailability of the final drug product.

Original languageEnglish
JournalMolecular Pharmaceutics
Issue number5
Pages (from-to)1598–1603
Publication statusPublished - 2022

Bibliographical note

Funding Information:
We acknowledge the Independent Research Fund Denmark [grant no. 8022-00154B and grant no. 8021-00339B] as well as the Villum Foundation [grant no. 17387] for financial support.

Publisher Copyright:
© 2022 American Chemical Society.

    Research areas

  • atomic force microscopy, dissolution, molecular crystals, molecular dynamics simulation, pH, surface mobility

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