Preparation and Characterization of Isosorbide Mononitrate Hydrogels Obtained by Free-Radical Polymerization for Site-Specific Delivery

Purpose: To prepare and characterize acrylic acid and ethyl cellulose hydrogels of isosorbide mononitrate for site-specific delivery.
Methods: Free radical polymerization method was employed using benzoyl peroxide as initiator and N, N'-Methylenebisacrylamide (MBA) crosslinked copolymer of ethyl cellulose and acrylic acid. Benzyl peroxide and N, N'-Methylenebisacrylamide in varying amounts were dissolved in acrylic acid. The two solutions were mixed together to a final weight of 100 g. Hydrogels were evaluated for sol-gel characteristics, diffusion coefficient, and porosity. Hydrogel formation was examined by FTIR while drug loading efficiency study was carried out using 1 % (w/v) drug solution.
Results: Swelling and drug release decreased with increasing acrylic acid and MBA concentrations due to high degree of crosslinking. Increasing acrylic acid content of hydrogel produced a decrease in drug release from 29.89 to 25.79 %, 75.37 to 67.87 % and 84.91 to 75.85 % at pH 1.2, 6.5 and 7.5, respectively. Remarkably, high swelling was observed at higher pH. Gel fraction and porosity results showed that acrylic acid and crosslinker raised gel fraction but reduced porosity, while ethyl cellulose exhibited a reverse effect. FTIR confirmed graft copolymer formation.
Conclusion: Isosorbide mononitrate hydrogels prepared with crosslinked copolymer of ethyl cellulose and acrylic acid can be suitably formulated for targeted delivery of the drug to the small intestine.

Keywords
N; N'-Methylenebisacrylamide; Ethyl cellulose; Acrylic acid; Isosorbide mononitrate; Free radical polymerization; Graft copolymer; Site-specific delivery; Hydrogel; pH-sensitive