Effect of pH on the Surface Layer of Molecular Crystals at the Solid-Liquid Interface
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Effect of pH on the Surface Layer of Molecular Crystals at the Solid-Liquid Interface. / Herzberg, Mikkel; Larsen, Anders S.; Hassenkam, Tue; Madsen, Anders; Rantanen, Jukka.
In: Molecular Pharmaceutics, Vol. 19, No. 5, 2022, p. 1598–1603.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Effect of pH on the Surface Layer of Molecular Crystals at the Solid-Liquid Interface
AU - Herzberg, Mikkel
AU - Larsen, Anders S.
AU - Hassenkam, Tue
AU - Madsen, Anders
AU - Rantanen, Jukka
N1 - 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.
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
KW - atomic force microscopy
KW - dissolution
KW - molecular crystals
KW - molecular dynamics simulation
KW - pH
KW - surface mobility
U2 - 10.1021/acs.molpharmaceut.2c00087
DO - 10.1021/acs.molpharmaceut.2c00087
M3 - Journal article
C2 - 35451842
AN - SCOPUS:85129304398
VL - 19
SP - 1598
EP - 1603
JO - Molecular Pharmaceutics
JF - Molecular Pharmaceutics
SN - 1543-8384
IS - 5
ER -
ID: 306592693