Issue 19, 2024

Anti-plasticizing effect of water on prilocaine and lidocaine – the role of the hydrogen bonding pattern

Abstract

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[double bond, length as m-dash]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.

Graphical abstract: Anti-plasticizing effect of water on prilocaine and lidocaine – the role of the hydrogen bonding pattern

Supplementary files

Article information

Article type
Paper
Submitted
06 Marts 2024
Accepted
29 Apr. 2024
First published
07 Maijs 2024

Phys. Chem. Chem. Phys., 2024,26, 14149-14159

Anti-plasticizing effect of water on prilocaine and lidocaine – the role of the hydrogen bonding pattern

X. Xu, H. Grohganz and T. Rades, Phys. Chem. Chem. Phys., 2024, 26, 14149 DOI: 10.1039/D4CP00995A

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements