Comparative evaluation of coprecipitation, solvent evaporation, and kneading as techniques to improve solubility and dissolution profiles of a BCS class IV drug

Abstract

Purpose Furosemide bioavailability is limited by poor solubility and permeability. This study aimed to compare coprecipitation, kneading, and solvent evaporation as solubility and dissolution improvement techniques. Materials and methods Products were prepared with furosemide : polyvinylpyrrolidone : lactose at 1 : 1 : 2, 1 : 2 : 3, 1 : 3 : 4, 1 : 1 : 4, 1 : 2 : 6, 1 : 3 : 8 by coprecipitation, kneading, solvent evaporation or physical blending. They were characterized for physicochemical properties and interaction. Solubilities of furosemide from products were evaluated in water and n-octanol. Dissolution studies on the products were conducted in 0.1 N HCl using USP apparatus II. Results Solubility of pure furosemide was lowest in n-octanol (11.86 μg/ml) and highest in PBS (28.68 μg/ml). Infrared spectra revealed that characteristic peaks in pure furosemide were retained in its formulations, indicating chemical compatibility of furosemide and the excipients. Differential scanning calorimetry thermogram of furosemide showed a melting point at 220°C, which disappeared in its formulations − attributable to amorphization of the drug or overshadow by excipients. Furosemide significantly partitioned more (P kneading>physical mixtures>coprecipitation. Cumulative amount of furosemide dissolved from pure sample was 8%, whereas amounts from formulations were significantly higher (P Conclusion All the methods improved the solubilities and dissolution profiles of furosemide to various degrees; however, solvent evaporation method was the best.