Preparation and characterization of an alginate-chitosan hydrogel with ibuprofen dissolved in the betaine-sorbitol deep eutectic solvent

Ibuprofen is one of the most commonly used pharmaceutical active ingredients for relieving pain, inflammation, and high fever. Its application is limited due to poor solubility in intestinal fluids, which results in lower bioavailability after oral administration. Organic solvents can dissolve it, but the main challenge is their toxic effects on the human body. For these reasons, eutectic solvents have been intensively investigated as safe and eco-friendly alternatives to pharmaceutical solvents. This study aimed to assess the feasibility of using the betaine-sorbitol (1:1 mol/mol) eutectic solvent to improve the solubility of ibuprofen. To reduce viscosity, water was added to the eutectic solvent in a 1:3 (v/v) ratio. This solvent increased the solubility of ibuprofen by approximately 7,800 times at 25 °C compared to water. Due to severe gastrointestinal side effects, the long-term oral use of ibuprofen is limited. Therefore, an alginate-chitosan hydrogel containing the drug, dissolved in an eutectic solvent, was prepared and characterized. The hydrogel formulation was prepared using 1.5% (w/v) aqueous alginate solution, 2% (w/v) calcium chloride, and 0.5% (w/v) chitosan dissolved in 0.5% (v/v) acetic acid. The encapsulation efficiency of ibuprofen in the hydrogel was found to be 82.5%. The hydrogel's swelling ability was tested by immersing it in simulated gastric fluid (pH 1.2) for 2 h, followed by simulated intestinal fluid (pH 7.4) for a further 6 h, resulting in a swelling degree of 2,212%. The in vitro release profile of ibuprofen from the hydrogel in simulated intestinal fluids at 37 °C was kinetically analyzed and concluded that the release followed the Korsmeyer-Peppas model. After 8 h, a high percentage of ibuprofen release (92.7%) was achieved from the hydrogel matrix.