Quetiapine Fumarate Loaded Nanostructured Lipid Carrier for Enhancing Oral Bioavailability: Design, Development and Pharmacokinetic Assessment
Shweta Agarwal, S L Harikumar, Poonam Negi, Navneet Kumar Upadhyay, Rajeev Garg
Abstract
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 lymphatic uptake. 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: 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.