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

Okoye, Ebere I.; Ezenwa, Chizoba G.; Aburime, Ome I.; Ekweogu, Austinline C.

doi:10.4103/epj.epj_7_17

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

Authors

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 -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 -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 (<0.05) into water than into -octanol. Batch 1 : 3 : 4 formulations gave the best partitioning of drug into the solvents, and was in the following order: solvent evaporation>kneading>physical mixtures>coprecipitation. Cumulative amount of furosemide dissolved from pure sample was 8%, whereas amounts from formulations were significantly higher (<0.05). Coprecipitation products displayed the poorest profiles, kneading gave better profiles, but lagged behind solvent evaporation, whose products’ dissolution profiles were significantly better (<0.05) than other products studied.
Conclusion
All the methods improved the solubilities and dissolution profiles of furosemide to various degrees; however, solvent evaporation method was the best.

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