The Role of Hydrogen Bonding in Paracetamol-Solvent and Paracetamol-Hydrogel Matrix Interactions

Abstract

The photophysical and photochemical properties of antipyretic drug - paracetamol (PAR) and its two analogs with different substituents (acetanilide (ACT) and N-ethylaniline (NEA)) in 14 solvents of different polarity were investigated by the use of steady-state spectroscopic technique and quantum-chemical calculations. As expected, the results show that the spectroscopic behavior of PAR, ACT, and NEA is highly dependent on the nature of the solute-solvent interactions (non-specific (dipole-dipole) and specific (hydrogen bonding)). To characterize these interactions, the multiparameter regression analysis proposed by Catalán was used. In order to obtain a deeper insight into the electronic and optical properties of the studied molecules, the difference of the dipole moments of a molecule in the ground and excited state were determined using the theory proposed by Lippert, Mataga, McRae, Bakhshiev, Bilot, and Kawski. Additionally, the influence of the solute polarizability on the determined dipole moments was discussed. The results of the solvatochromic studies were related to the observations of the release kinetics of PAR, ACT, and NEA from polyurethane hydrogels. The release kinetics was analyzed using the Korsmayer-Peppas and Hopfenberg models. Finally, the influence of the functional groups of the investigated compounds on the release time from the hydrogel matrix was analyzed.

Keywords: drug release; hydrogel matrix; hydrogen bond; paracetamol; solvatochromism; solvent effects.

Figure 1

Chemical structure of (a) paracetamol (PAR), (b) acetanilide (ACT), (c) N-ethylaniline (NEA), and (d) fragment of the structure of the polyurethane hydrogel matrix chain.

Figure 2

The long-wavelength absorption and fluorescence spectra of (a) PAR, (b) ACT and (c) NEA in solvents of different polarity: cyclohexane (CH, black straight line), diethyl ether (DE, red dashed line), and in deionized water (H${}_2$O, blue dotted line).

Figure 3

Positions of the long-wavelength absorption ($\widetilde{{\nu }_a}$) and fluorescence ($\widetilde{{\nu }_f}$) bands as a function of E${}_N^T$ parameter.

Figure 4

Position of the long-wavelength absorption and fluorescence bands of (a) PAR, (b) ACT, and (c) NEA obtained according to Catalán model ( ${\tilde{\nu }}_{a,f}^{\mathit{theor}}$) versus the corresponding experimental $\widetilde{{\nu }_a}$ and $\widetilde{{\nu }_f}$ values. The relative (percentage) contribution of non-specific and specific interactions is presented in the inset of Figure 4.

Figure 5

Stokes shifts ($\widetilde{{\nu }_a}-\widetilde{{\nu }_f}$) versus the solvent polarity functions ($f_{MR}(\epsilon ,n)$, $f_B(\epsilon ,n)$, $f_{LM}(\epsilon ,n)$) for three tested molecules: (a) paracetamol (PAR), (b) acetanilide (ACT), and (c) N-ethylaniline (NEA).

Figure 6

Changes in absorption spectra of (a) PAR, (b) ACT, and (c) NEA during release from PU/polyethylene glycol (PEG) 4000 hydrogel at room temperature (25 °C).

Figure 7

Changes in molar concentration (C) of (a) PAR, (b) ACT, and (c) NEA released from PU/PEG hydrogels at 25 °C (black circles) and at 37 °C (blue circles). The solid lines represent the fitted theoretical models.

Figure 8

Three possible interactions of a PAR molecule with a hydrogel matrix.