Aims: The study aimed at developing and characterizing Nanostructured Lipid Carriers (NLC)
of Quetiapine Fumarate (QF) by Design of Experiment (DoE) for the enhancement of bioavailability.
Background: QF, an anti-psychotic drug, has an oral bioavailability of 9% due to hepatic first- pass
metabolism necessitating the use of high doses. Its side effects are dose -related and enhancement in
bioavailability would result in minimization of side effects.
Objective: The objective of the study was the enhancement of bioavailability of the NLC of QF by preferential
Methods: Hot emulsification-ultrasonication was the method of formulation using PrecirolATO5 and
Oleic acid as solid and liquid lipids respectively. Poloxamer188 and Phospholipon90G were used as
surfactant and stabilizer respectively. Solid:liquid lipid ratio and Phospholipon90G amount were independent
variables and percent Entrapment Efficiency (%EE), Particle Size (PS) dependent variables
during optimization by Central Composite Design.
Results: The optimized formulation showed a %EE of 77.21%, PS of 140.2 nm and surface charge of -
19.9mV. Higuchi kinetic model was followed during the in-vitro release. TEM revealed spherical,
smooth nanoparticles. A pharmacokinetic study in rats showed AUC0-∞ of QF-NLC to be 3.93 times
that of QF in suspension, suggesting significant enhancement in bioavailability. An increase in AUC0-∞
in cycloheximide untreated rats’ group of QF-NLC by 2.43 times as compared to cycloheximide treated
group, confirmed lymphatic absorption of QF- NLC.
Conclusion: The results validated DoE as an appropriate tool for developing QF loaded NLC and
proved NLC to be a promising delivery system for the enhancement of oral bioavailability of QF.