Design of polyacrylamide grafted sesbania gum-mediated pH-responsive IPN-based microbeads for delivery of diclofenac sodium: In-vitro-in-vivo characterizations
Pratiksha Devkar, Sopan Nangare, Laxmikant Zawar, Nitin Shirsath, Piyush S. Bafna, Pankaj Jain
Abstract
Microwave-assisted grafting of polyacrylamide on sesbania gum (PAAM-g-SG) was implemented employing a 3 2 full factorial experimental design and was hydrolyzed using sodium hydroxide (NaOH) to form H-PAAM-g-SG. Further, the diclofenac sodium-loaded novel pH-sensitive interpenetrating polymeric network (IPN) microbeads were designed using an optimized H-PAAM-g-SG and sodium alginate (SA). Different spectroscopic analysis including FTIR spectroscopy , 1 H NMR spectroscopy, elemental analysis , thermal analysis, etc. was performed to confirm the synthesis of PAAM-g-SG and diclofenac-loaded pH-sensitive IPN H-PAAM-g-SG-SA microbeads. Here, Ca +2 ions combine with two strands of SA and form a round-shape structure that encloses uncross-linked H-PAAM-g-SG polymer and diclofenac sodium. As well, glutaraldehyde (GL) addition improved the mechanical strength due to acetal structure between hydroxyl of H-PAAM-g-SG and aldehyde of GL. The drug entrapment was confirmed proportional relationship to the Ca +2 ions concentration whereas an increase in GL concentration resulted in a reduced drug entrapment. The pH pulsatile study assured the reversible swelling-shrinkage behavior of IPN microbeads due to the carboxyl group of PAAM-g-SG. The drug release from H-PAAM-g-SG-SA microbeads (batch: S9) was found to be 84.21 % (12 h ) which was non-significant ( p > 0.05; f2 = 79 ∼ 90) over marketed formulation (83.31 %). Moreover, it follows the Korsmeyer Peppas (R 2 = 0.996) as the best-fit release kinetic model. The pH-sensitive release of diclofenac sodium from IPN H-PAAM-g-SG-SA microbeads was assured based on in vivo anti-inflammatory activity ( p < 0.05). Therefore, developed novel pH-sensitive IPN microbeads based on H-PAAM-g-SG are a promising polymeric carrier substitute for delivery of drugs actuated by a pH stimulus.