Synthesis of pH-sensitive hydrogel beads for controlled delivery of ketorolac tromethamine: computational evaluation and in vivo pharmacokinetic study.

The current study aimed to develop pH-responsive hydrogel beads based on sodium alginate (SA) and acrylic acid (Aa), crosslinked in the presence of calcium chloride, for the controlled delivery of ketorolac tromethamine. The hydrogel beads were fabricated using the ionic gelation technique and subsequently characterized for their structural properties, surface morphology, and thermal stability. Additional investigations, including sol-gel analysis, drug loading efficiency, and drug quantification, were conducted to evaluate the physicochemical attributes of the prepared beads. Furthermore, Monte Carlo simulations using the adsorption locator module in Materials Studio were conducted to investigate the adsorption behavior of ketorolac on the SA/Aa hydrogel beads. The negative adsorption energy obtained from the simulations suggested that the interaction between the drug and polymer was both spontaneous and exothermic, indicating a thermodynamically favorable binding mechanism. The pH responsiveness of the beads was evaluated through swelling and drug release studies under different pH conditions (pH 1.2 and 7.4). The results indicated markedly significant swelling and drug release at pH 7.4 as compared to 1.2, thereby confirming the pH-responsive behavior of the formulated beads. The toxicity of the hydrogel beads was evaluated using the Hen's Egg Test on Chorioallantoic Membrane (HET-CAM), which revealed no signs of irritation or toxicity. An in vivo pharmacokinetic study in rabbits further demonstrated that the drug-loaded hydrogel beads achieved higher plasma concentrations of ketorolac tromethamine compared to the drug solution, supporting their potential for improved bioavailability. Hence, the developed SA/Aa-based hydrogel beads exhibited favorable physicochemical, biocompatibility, and pharmacokinetic profiles, making them promising candidates for controlled drug delivery systems.