Pharmacokinetics, tissue distribution and bioavailability of clozapine solid lipid nanoparticles after intravenous and intraduodenal administration.

摘要: Clozapine, a lipophilic effective atypical antipsychotic drug, has very poor oral bioavailability (<27%) due to first pass effect. Clozapine solid lipid nanoparticles have been developed using various triglycerides (trimyristin, tripalmitin and tristearin), soylecithin 95%, poloxamer 188 stearylamine as positive charge inducer by hot homogenization followed ultrasonication method. Particle size measurements were made with Malvern Zetasizer. Pharmacokinetics of clozapine incorporated in (SLNs), after intravenous (i.v.) administration conscious male Wistar rats studied. The aim this research was find out whether the can be improved administering SLN duodenally rats. Tissue distribution studies suspension carried Swiss albino mice. Average zeta potential SLNs different lipids ranged from 96.7+/-3.8 163.3+/-0.7 nm 21.3+/-1.3 33.2+/-0.6 mV, respectively. AUC((0-infinity)) increased (up 2.91-fold) clearance decreased 2.93-fold) when entrapped administered intravenously. Bioavailability 2.45- 4.51-fold intraduodenal compared that suspension. In tested organs, AUC MRT higher than those especially brain reticuloendothelial cell-containing organs. These results indicate are suitable drug delivery system for improvement drugs such clozapine.