Synthesis, Characterization and Swelling Kinetics of Co-polymeric Hydrogels

Abstract

Copolymers of methacrylate (MA), vinyl acetate (VA), acrylic acid (AA) and N-isopropylacrylamide (NiPAAm) were synthesized in various combinations through free radical polymerization method. The co-polymers were characterized using different techniques including FTIR, DSC/TGA and rheology. Swelling parameters i.e. dynamic and equilibrium media sorption, media penetration velocity, swelling mechanism and diffusion exponent (n) were investigated with respect to the nature of cross-linker (EGDMA or DEGDMA), concentration of the cross-linking agent and acrylic acid. Stimuli-responsiveness of these hydrogels was determined analyzing the effect of change in media pH on swelling behavior. Based on preliminary swelling studies, Tramadol HCl, the model drug was loaded in selected batches of co-polymeric hydrogels under optimized conditions of pH (8.0) and temperature (37oC). The drug release studies of these hydrogels were carried out in phosphate buffer solution of pH 8.0 and at 37oC, using a UV/Visible spectrophotometer. Various models were applied to interpret the drug release kinetics of the co-polymeric hydrogels. Using equilibrium swelling data, network parameters i.e. Vs, Mc, q etc. were calculated applying Flory-Rehner equation. Rheological characterization was carried out to explore flow behavior of Poly (MA-co-VA-co-AA) physically cross-linked hydrogels, at a temperature range of 10-37oC. The data obtained were modulated using different models. It was found that the rate of media sorption and equilibrium media sorbed through these hydrogels could be fairly controlled changing the composition of co-polymers and swelling conditions say pH and temperature. Most of synthesized hydrogels had a good correlation coefficient with the second order kinetic model in acidic medium and first order kinetics in basic pH except NiPAAm gels which mostly followed Schott’s model in preference to Maxwell- 9 Peppas approach. The hydrogels Poly (MA-co-VA-co-AA) showed Fickian swelling mechanism (n<0.5) in pH below pKa of AA (4.75) and non-Fickian behavior (0.5<n<1) above pKa of AA, whereas NiPAAm gels underwent non-Fickian mechanism at all media pH values. Media penetration velocity and equilibrium media content seemed to have a good correlation coefficient with each other in all synthesized hydrogels. These co-polymeric systems had an excellent capacity to absorb and retain the model drug within their network. It was found that the drug loading and unloading capacity of the systems decreased with the concentration of the cross-linker and improved with higher initial drug concentration. The gels followed predominantly the first order drug release kinetics. The chemically cross-linked Poly (MA-co-VA-co-AA) presented non-Fickian drug release mechanism, but in the NiPAAm co-polymeric hydrogels, Fickian behavior was dominant. It was observed that less concentration of the cross-linking agent, higher amount of AA and the basic medium improved the molecular weight between the cross-links, Mc and reduced the volume fraction of the polymer, Vs. Rheological studies revealed that Poly (MA-co-VA-co-AA) had a threshold concentration of AA after that the gels violated the general trends of yield stress (γ), fluidity index (n) and consistency coefficients (k). These gels showed pseudo-plastic behavior (n<1). Good mechanical strength and promising ability of drug loading and the release in the chemically cross-linked Poly (MA-co-VA-co-AA) in basic medium indicate that these drug carriers are capable to resist peristaltic pressure of gastrointestinal tract (GIT) and the acidic medium of stomach thus may be used as colon-specific drug delivery systems. The rheological analysis of physically cross-linked Poly (MA-co-VA-co-AA) favors these systems to be used as topogels. Moreover, shift of lower critical temperature from 32oC to 33.6oC by the incorporation of a good balance of hydrophobic and hydrophilic components with N-isopropylacrylamide in co-polymeric hydrogels made them suitable to be loaded with the drug at room temperature and release the drug at 37oC, human body temperature.