SYNTHESIS, CHARACTERIZATION AND IN VIVO EVALUATION OF PH SENSITIVE HYDROXYPROPYL METHYL CELLULOSE-GRAFT-ACRYLIC ACID HYDROGELS FOR SUSTAINED DRUG RELEASE OF MODEL DRUG NICORANDIL

Background: Anti hypertensive drugs like “Nicorandil” require frequent dosing due to their shorter half-life. Such drugs are also pH sensitive, due to which greater portions of these drugs are degraded in acidic pH of stomach resulting in lesser bioavailability. The objective of this study was to formulate graft polymeric carrier system for sustained delivery of nicorandil to minimize dosing frequency and enhance patient compliance. Materials Methods: This animal model study was conducted in Department of Pharmacy, Islamia University of Bahawalpur, Pakistan. Hydroxypropyl methyl cellulose-graft-acrylic acid hydrogels were synthesized by free radical solution polymerization with diverse weight ratios of polymer, monomer and cross linker. Total duration of study was 1.5 years from March 2013 to August 2015. The N, N-methylene bis acrylamide and potassium persulfate were used as crosslinker and initiator respectively. Hydrogels were characterized for swelling ratio, equilibrium swelling, gel content, porosity and in vitro drug release. The surface morphology of synthesized hydrogels was evaluated by using Scanning Electron Microscopy. Thermal properties of hydrogels were evaluated by Thermogravimetric Analysis and Differential Scanning Calorimetry whereas FTIR was done to examine chemical compatibility. Finally, in vivo evaluation of prepared hydrogels was carried out in rabbits using simple parallel study design to estimate various pharmacokinetic parameters.Results: HPMC-co-AA hydrogels had good pH sensitivity whereas; they demonstrated maximum and minimum swelling at pH 7.4 and 1.2 respectively. Swelling ratio, gel fraction and cumulative percent drug release were decreased with increasing crosslinker concentration while these parameters were increased with increasing AA and HPMC concentrations. A porous network was observed in the SEM images. All formulation ingredients of prepared hydrogels showed good compatibility as determined by FTIR. Results of in vivo study proved the pH sensitivity and sustained drug release of prepared hydrogels.Conclusion: The HPMC-graft-AA hydrogels showed good pH-sensitivity and sustained-release profile for model drug nicorandil.