Norfloxacin mixed solvency based solid dispersions: An in-vitro and in-vivo investigation

Abstract

Norfloxacin (NF) is a synthetic fluoro-quinolone molecule that is used for the treatment of urinary tract infections. However, due to its poor aqueous solubility, it has low oral bioavailability. The aim of the present study was to improve the aqueous solubility and dissolution profile of NF by formulating its mixed-solvency based solid dispersions (SDs). The NF-loaded SDs were prepared by a solvent evaporation technique using urea, sodium benzoate and a niacinamide hydrotropic mixture. The prepared SDs were evaluated regarding their solubility, mean particle size, in-vitro drug release and oral bioavailability. The optimized batch showed a high percentage yield of 99.04% , with a mean particle size of 132.91 μm. Optimized SDs Exhibit 96.48% drug release. The oral bioavailabilities of NF from the optimized SDs, drug alone and marketed formulation were evaluated in Wistar rats at a dose of 20.0 mg/kg. In comparison to the drug alone, approximately 6.90- and 5.0-fold increases in AUC and Cmax, respectively, were observed for NF from mixed-solvency based SDs. The superior dissolution rate due to its reduced particle size may have contributed to the increased oral bioavailability. This study demonstrated that mixed-solvency may be an alternative approach for poorly soluble drugs to improve their solubility and oral bioavailability.