Effect of precipitation inhibitors on supersaturation and solubility of furosemide

Abstract

Furosemide is a widely used diuretic drug for the treatment of edema associated with heart, liver cirrhosis, renal diseases and hypertension. It is a Class IV drug with low aqueous solubility and low permeability according to Biopharmaceutics Classification System (BCS). Furosemide was chosen as a model drug to examine the effect of polymeric precipitation inhibitors (PPIs) on the supersaturation and solubility. Solubility and concentration change of furosemide as a function of time at pH 1.2 and 6.8 were determined to show the effects of PPIs on furosemide solubility. The 24 h equilibrium solubility of furosemide was 0.017 +/- 0.004 and 3.62 +/- 0.201 mg/mL at pH 1.2 and pH 6.8 buffer solutions, respectively. PPI type and concentration (0.05%, 0.25%) did not increase furosemide solubility at pH 1.2. However, both hydroxypropylmethylcellulose (HPMC) and polyvinylpyrrolidoneK17 (PVPK17) at two concentrations increased furosemide solubility at pH 1.2 and 6.8. In addition, viscosity of solutions was in the range of 2.2-3.7 centipoise, and it was not influenced by PPIs concentrations. Our results showed that designing supersaturated formulations using PPIs can be useful and promising to enhance solubility of furosemide.