Quetiapine fumarate loaded nanostructure lipid carrier for enhancing oral bioavailability: Design, development and pharmacokinetic assessment.

AIM: The study aimed at developing and characterizing nanostructure lipid carriers (NLC) of Quetiapine fumarate (QF) by Design of Experiment (DoE) for enhancement of bioavailability.
BACKGROUND: QF, an anti-psychotic drug, has oral bioavailability of 9% due to hepatic first pass metabolism necessitating 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 enhancement of bioavailability of NLC of QF by preferential lymphatic uptake.
METHODS: Hot emulsification-ultrasonication was the method of formulation using PrecirolATO5 and Oleic acid as solid and liquid lipid 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 %EE of 77.21%, PS of 140.2nm and surface charge of -19.9mV. Higuchi kinetic model was followed during in-vitro release. TEM revealed spherical, smooth nanoparticles. X-ray diffraction study con-firmed presence of drug in amorphous state in NLC. 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 cyclo-heximide untreated rats group of QF loaded NLC by 2.43 times ascompared 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 enhancement of oral bioavailability of QF. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.