Nanoprecipitation with sonication for enhancement of oral bioavailability of furosemide.
Furosemide is a weakly acidic diuretic indicated for treatment of edema and hypertension. It has very poor solubility but high permeability through stomach and upper gastrointestinal tract (GIT). Due to its limited solubility it has poor and variable oral bioavailibility of 10-90%. The aim of this study was to enhance the oral bioavailibilty of furosemide by preparation of nanosuspensions. The nanosuspensions were prepared by nanoprecipitation with sonication using DMSO (dimethyl sulfoxide) as a solvent and water as an antisolvent (NA). The prepared nanosuspensions were sterically stabilized with polyvinyl acetate (PVA). These were characterized for particle size, zeta potential, polydispersity index, scanning electron microscopy (SEM), differential scanning calorimetry (DSC), X-ray diffraction (XRD) pattern and release behavior. The average particle size of furosemide nanoparticles were found to be in the range of 150-300 nm. This was further confirmed by SEM photograph. The particle size varies with an increase in concentration of drug and stabilizer. The preparations showed negative zeta potential and polydispersity index in the range of 0.3 +/- 0.1. DSC and XRD studies indicated that the crystalline furosemide drug was converted to amorphous form upon precipitation into nanoparticles. The saturation solubility of prepared furosemide nanoparticles markedly increased compared to the original drug in simulated gastric fluid. The release profiles of nanosuspension formulation showed up to 81.2% release in 4 h. It may be concluded that the nanoprecipitation with ultrasonication have potential to formulate homogenous nanosuspensions with uniform sized amorphous nanoparticles of furosemide. Polyvinyl acetate can be used as a suitable steric stabilizer to prepare stable furosemide nanosuspensions. The enhanced saturation solubility in simulated gastric fluid may lead to enhanced absorption of furosemide.
Bhanu P
BP
Sahu
Malay K
MK
Das
D000284:Administration, Oral; D001682:Biological Availability; D002152:Calorimetry, Differential Scanning; D011232:Chemical Precipitation; D005665:Furosemide / Q000737:chemistry / Q000493:pharmacokinetics*; D008855:Microscopy, Electron, Scanning; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D014961:X-Ray Diffraction
D005665:Furosemide