Nanoparticles for improving the dissolution and oral bioavailability of spironolactone, a poorly-soluble drug

Nanoparticles of spironolactone (Sp), a model of poorly water-soluble drugs, were prepared via two techniques: emulsification-solvent evaporation (ESE) and emulsification-solvent diffusion (ESD), using lecithin (Le) and sodium glycocholate (SGC) or PVP as emulsifiers. The nanoparticles were evaluated with respect to particle size, drug content, in vitro dissolution and bioavailability in beagle dogs. The results revealed that the ESE technique enabled to prepare Sp as nanoparticles with a mean diameter of 112 and 186 nm using Le-SGC (4/1) and Le-PVP (4/10), respectively. However, in the case of the ESD technique, the nanoparticles had a mean diameter of 134 and 215 nm with the same emulsifiers. The type and concentration of emulsifiers, in addition to the method of preparation, had significant effects on the drug content within the nanoparticles. The initial dissolution rate of Sp nanoparticles (within the first 10 min) was increased by about 70-fold and 60-fold in the case of nanoparticles prepared with Le-SGC by ESE and ESD methods, respectively. However, as regards nanoparticles prepared with Le-PVP, the dissolution rate was increased by about 67-fold and 54-fold, respectively. The bioavailability of Sp nanoparticles of 112 nm compared with the conventional Sp (untreated) was studied in beagle dogs. A 15-fold (approximately) increase in the C of canrenone (a major metabolite of Sp) was observed while the AUC 0-24 and AUC 0- ∞ were increased by 10.