Preparation, Characterization and Study of the Dissociation of Naproxen from Its Chitosan Salt

Abstract

Salts of naproxen (NAP) with chitosan (CTS) and reticulated chitosan (CEP) were prepared under optimized conditions to maximize the yield of reaction. The objective was to evaluate the dissociation in water, which can guide studies of release of the drug from biopolymeric salts in pharmaceutical applications. Higher salification was found after 24 h of reaction at 60 °C in a molar ratio 1:1.05 (CTS:NAP, mol/mol), resulting in a degree of substitution (DS) of 17% according to 13C NMR, after neutralization of the –NH2 group of the biopolymer by the carboxylic group of the drug. The presence of NAP salt is evidenced by FTIR bands related to the –NH3+ group at 856 cm−1, a decrease in crystallinity index in XRD diffractograms as well as changes in mass loss ratios (TG/DTG/DTA) and increased thermal stability of the salt regarding CTS itself. The CEPN crosslinked salt presented a DS = 3.6%, probably due to the shielding of the –NH2 groups. Dissociation studies revealed that at pH 2.00, dissociation occurred faster when compared to at pH 7.00 in the non-reticulated salt, while the opposite was observed for the reticulated one.