Diffusion and binding of 5-fluorouracil in non-ionic hydrogels with interpolymer complexation

Abstract

Hydrogen-bonded interpolymer complexes can be used for development of novel dosage forms. In this study, two types of crosslinked hydrogels, copolymer networks of N-vinyl pyrrolidone and acrylamide (PVP-co-PAM) and interpenetrating polymer networks (IPN) composed of crosslinked PVP-co-PAM and poly(vinyl alcohol) (PVA), were synthesized at three different degrees of crosslinking. The side chain groups in such polymers can form non-ionic complexes through H-bonding, resulting in additional “crosslinks” in the hydrogels. Both kinds of hydrogels have significantly larger swelling sensitivities than the networks formed with ionizable side chains. In the IPNs, introduction of the PVA chains into the PVP-co-PAM networks raises the permeability, indicating more open pores. The permeability decreases with the increasing degree of crosslinking of the copolymer. For probing the drug binding in the hydrogels, Fourier transform infrared spectra (FTIR) difference spectroscopy indicated the presence of significant H-bonding interactions between 5-fluorouracil (5-FU) and the side chains of the polymers. Such interactions are larger in the PVP-co-PAM copolymers than in the IPN hydrogels, thereby causing an additional source of the slower release kinetics in the copolymer hydrogels as revealed by the Peppas model, albeit both types of the networks followed a non-Fickian transport mechanism.