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

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 processis essentially controlled by activity at the surface of the molecular crystals, which is difficult tocharacterize experimentally. To address this, a combination ofin situatomic force microscopy(AFM) with molecular dynamics (MD) simulation is reported. AFM allows for directvisualization of the crystal surface of basic and acidic model compounds (carvedilol andibuprofen) in contact with an aqueous medium with varying pH. A dramatic increase in surfacemobility in the solid-liquid interface could be observed experimentally as a function of pH. Thein situAFM approach opens up for a more detailed understanding of the behavior of particulatematter in solution with importance at different levels, ranging from engineering aspects relatedto crystallization, and biological considerations related to bioavailability of the final drug product

Automated summary

The dissolution of solid matter into aqueous solution is a challenging aspect in drug development, with pH being the most important factor. The combination of in situ atomic force microscopy (AFM) and molecular dynamics simulation allows for direct visualization of the crystal surface and provides a more detailed understanding of the behavior of particulate matter in solution.