Formulation and optimization of solid lipid nanoparticles of buspirone HCl for enhancement of its oral bioavailability.
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 L(8) 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.
Varshosaz
Jaleh
J
Department of Pharmaceutics, Faculty of Pharmacy and Isfahan Pharmaceutical Sciences Research Center, Isfahan University of Medical Sciences, Isfahan, Iran. varshosaz@pharm.mui.ac.ir
Tabbakhian
Majid
M
Mohammadi
Mahboobeh Y
MY
D000284:Administration, Oral; D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry / Q000493:pharmacokinetics; D001682:Biological Availability; D002065:Buspirone / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D008055:Lipids / Q000737:chemistry*; D008297:Male; D008422:Materials Testing; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D051381:Rats; D017208:Rats, Wistar; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics
D001672:Biocompatible Materials; D008055:Lipids; D017366:Serotonin Receptor Agonists; D002065:Buspirone