Anti-plasticizing effect of water on prilocaine and lidocaine: the role of the hydrogen bonding pattern
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Anti-plasticizing effect of water on prilocaine and lidocaine : the role of the hydrogen bonding pattern. / Xu, Xiaoyue; Grohganz, Holger; Rades, Thomas.
In: Physical Chemistry Chemical Physics, Vol. 26, 2024, p. 14149-14159.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Anti-plasticizing effect of water on prilocaine and lidocaine
T2 - the role of the hydrogen bonding pattern
AU - Xu, Xiaoyue
AU - Grohganz, Holger
AU - Rades, Thomas
N1 - Publisher Copyright: © 2024 The Royal Society of Chemistry.
PY - 2024
Y1 - 2024
N2 - It is generally accepted that water, as an effective plasticizer, decreases the glass transition temperatures (Tgs) of amorphous drugs, potentially resulting in physical instabilities. However, recent studies suggest that water can also increase the Tgs of the amorphous forms of the drugs prilocaine (PRL) and lidocaine (LID), thus acting as an anti-plasticizer. To further understand the nature of the anti-plasticizing effect of water, interactions with different solvents and the resulting structural features of PRL and LID were investigated by Fourier transform infrared spectroscopy (FTIR) and quantum chemical simulations. Heavy water (deuterium oxides) was chosen as a solvent, as the deuterium and hydrogen atoms are electronically identical. It was found that substituting hydrogen with deuterium showed a minimal impact on the anti-plasticization of water on PRL. Ethanol and ethylene glycol were chosen as solvents to compare the hydrogen bonding patterns occurring between the hydroxyl groups of the solvents and PRL and LID. Comparison of the various Tgs showed a weaker anti-plasticizing potential of these two solvents on PRL and LID. The frequency shifts of the amide C = O groups of PRL and LID due to the interactions with water, heavy water, ethanol, and ethylene glycol as observed in the FTIR spectra showed a correlation with the binding energies calculated by quantum chemical simulations. Overall, this study showed that the combination of weak hydrogen bonding and strong electrostatic contributions in hydrated PRL and LID could play an important role in inducing the anti-plasticizing effect of water on those drugs.
AB - It is generally accepted that water, as an effective plasticizer, decreases the glass transition temperatures (Tgs) of amorphous drugs, potentially resulting in physical instabilities. However, recent studies suggest that water can also increase the Tgs of the amorphous forms of the drugs prilocaine (PRL) and lidocaine (LID), thus acting as an anti-plasticizer. To further understand the nature of the anti-plasticizing effect of water, interactions with different solvents and the resulting structural features of PRL and LID were investigated by Fourier transform infrared spectroscopy (FTIR) and quantum chemical simulations. Heavy water (deuterium oxides) was chosen as a solvent, as the deuterium and hydrogen atoms are electronically identical. It was found that substituting hydrogen with deuterium showed a minimal impact on the anti-plasticization of water on PRL. Ethanol and ethylene glycol were chosen as solvents to compare the hydrogen bonding patterns occurring between the hydroxyl groups of the solvents and PRL and LID. Comparison of the various Tgs showed a weaker anti-plasticizing potential of these two solvents on PRL and LID. The frequency shifts of the amide C = O groups of PRL and LID due to the interactions with water, heavy water, ethanol, and ethylene glycol as observed in the FTIR spectra showed a correlation with the binding energies calculated by quantum chemical simulations. Overall, this study showed that the combination of weak hydrogen bonding and strong electrostatic contributions in hydrated PRL and LID could play an important role in inducing the anti-plasticizing effect of water on those drugs.
U2 - 10.1039/d4cp00995a
DO - 10.1039/d4cp00995a
M3 - Journal article
C2 - 38712380
AN - SCOPUS:85192492430
VL - 26
SP - 14149
EP - 14159
JO - Physical Chemistry Chemical Physics
JF - Physical Chemistry Chemical Physics
SN - 1463-9076
ER -
ID: 391932957