Preparation and characterization of hybrid pH-sensitive hydrogels of chitosan-co-acrylic acid for controlled release of verapamil

Abstract

In the present work crosslinked hydrogels based on chitosan (CS) and acrylic acid (AA) were prepared by free radical polymerization with various feed compositions using N,N methylenebisacrylamide (MBA) as crosslinking agent. Benzoyl peroxide was used as catalyst. Fourier transform infrared spectra (FTIR) confirmed the formation of the crosslinked hydrogels. This hydrogel is formed due to electrostatic interaction between cationic groups in CS and anionic groups in AA. Prepared hydrogels were used for dynamic and equilibrium swelling studies. For swelling behavior, effect of pH, polymeric and monomeric compositions and degree of crosslinking were investigated. Swelling studies were performed in USP phosphate buffer solutions of varying pH 1.2, 5.5, 6.5 and 7.5. Results showed that swelling increased by increasing AA contents in structure of hydrogels in solutions of higher pH values. This is due to the presence of more carboxylic groups available for ionization. On the other hand by increasing the chitosan content swelling increased in a solution of acidic pH, but this swelling was not significant and it is due to ionization of amine groups present in the structure of hydrogel. Swelling decreased with increase in crosslinking ratio owing to tighter hydrogel structure. Porosity and sol-gel fraction were also measured. With increase in CS and AA contents porosity and gel fraction increased, whereas by increasing MBA content porosity decreased and gel fraction increased. Furthermore, diffusion coefficient (D) and the network parameters i.e., the average molecular weight between crosslinks (M(c)), polymer volume fraction in swollen state (V(2s)), number of repeating units between crosslinks (M(r)) and crosslinking density (q) were calculated using Flory-Rehner theory. Selected samples were loaded with a model drug verapamil. Release of verapamil depends on the ratios of CS/AA, degree of crosslinking and pH of the medium. The release mechanisms were studied by fitting experimental data to model equations and calculating the corresponding parameters. The result showed that the kinetics of drug release from the hydrogels in both pH 1.2 and 7.5 buffer solutions was mainly non-Fickian diffusion.