Formulation and optimization of solid lipid nanoparticles of buspirone HCl for enhancement of its oral bioavailability

Abstract

Solid lipid nanoparticles (SLNs) of buspirone HCl as a water-soluble drug were prepared by emulsification-evaporation, followed by the sonification method. A preliminary screening of the most effective parameters on the production of nanoparticles by a Taguchi L8 orthogonal array showed that the lipid type, surfactant percentage, speed of homogenizer, and acetone:dichloromethane (DCM) ratio had a significant effect on particle size. In the next step, the lipid was fixed on cetyl alcohol, surfactant on Tween 20, lecithin:lipid weight ratio on 20:70, sonication time on 30 seconds, and the other effective, independent factors aforementioned were studied each at three levels by a three-factor, three-level Box-Behnken design. The percentage of drug entrapment, mean particle-size diameter, and zeta potential were studied as the responses. Contour plots were constructed to further elucidate the relationship between the independent and dependent variables. A pharmacokinetic study was conducted in male Wistar rats after oral administration of 15 mg.kg−1 buspirone in the form of free drug or SLNs. The optimized SLNs had aq particle size of 345.7 nm, loading efficiency of 32.8%, and zeta potential of −6.8 mV. Buspirone released about 90% during 4.5 hours in vitro. It was found that the relative bioavailability of the drug in SLNs was significantly increased, compared to that of the drug solution.