Furosemide is a Biopharmaceutical Classification System (BCS) Class IV diuretic whose bioavailability is strictly limited by its poor solubility and low permeability. This study aimed to optimize the cocrystallization of furosemide with malic acid as a coformer using the neat grinding method to enhance its solubility and dissolution rate. Optimization was performed using a Simplex Lattice Design (SLD) in Design-Expert 13.0 software. Furosemide (A) and malic acid (B) served as variables ranging from 1 to 2 molar ratios across eight experimental trials. Numerical analysis of saturation solubility and percentage of drug dissolved at 60 minutes (Q60) was conducted to identify the optimal ratio. Cocrystal formation by neat grinding significantly improved both the solubility and dissolution rate of furosemide. The optimal molar ratio of furosemide to malic acid was determined to be 1.339:1.661, achieving a desirability value of 0.965. The resulting optimized capsule formulation fully complied with standard physical properties and dissolution release parameters. In conclusion, neat grinding cocrystallization with malic acid at the optimized ratio effectively enhances the solubility and dissolution profile of furosemide, offering a novel approach for improved drug delivery.
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