Fabrication of pH responsive hydrogel blends of chondroitin sulfate/pluronic F-127 for the controlled release of ketorolac: its characterization and acute oral toxicity study

Drug Dev Ind Pharm. 2022 Nov 30;1-12. doi: 10.1080/03639045.2022.2150773. Online ahead of print.

Abstract

Objective: Ketorolac tromethamine (KT), selected as a model drug, is used in management of moderate to severe acute pain. It has a short half-life (∼5.5 h) and requires frequent dose administration when needed for longer period of time. In our current project, we designed pH responsive hydrogel blends of chondroitin sulfate/pluronic F-127 (CS/Pl) for the controlled release of ketorolac.

Methods: Hydrogel blends were fabricated using free radical polymerization reaction technique utilizing different ratios of chondroitin sulfate (CS) (polymer) and pluronic F-127 (polymer), acrylic acid (monomer), N,N'-methyl-bisacrylamide (MBA) (cross-linker), initiator ammonium persulfate (APS) and tween-80 (surfactant). The fabricated hydrogel blends were studied and evaluated for pH responsiveness, swelling, water absorbency, in vitro drug release, and morphological characteristics such as SEM, XRD, FTIR, and TGA/DSC. Acute toxicity study was performed on rabbits.

Results: Maximum swelling and water absorbency were shown by CS/Pl blends being significantly greater at 7.4 (basic pH) than in 1.2 (acidic pH). In vitro dissolution demonstrated pH responsive controlled KT release following zero order at higher pH (7.4) medium up to 36 h. FTIR studies confirmed the structures of our blends; SEM results showed porous framework; thermal studies revealed higher stability of hydrogels than the individual polymers; and XRD confirmed the nature of our blends. Toxicity study revealed the nontoxic nature of the hydrogel blends.

Conclusion: The prepared CS/Pl hydrogels demonstrated stimuli-controlled release with delivery of drug for prolonged period of time and thus can minimize dosing frequency, safe drug delivery, increased patient compliance and easiness.

Keywords: chondroitin sulfate; controlled release; free radical polymerization; ketorolac tromethamine; pH responsive.