Formulation and Development of In Situ Nasal Gelling Systems for Quetiapine Fumarate-Loaded Mucoadhesive Microemulsion

Purpose Quetiapine fumarate (QF), a novel antipsychotic agent, has got poor brain uptake because of its poor oral bioavailability (9 %) due to extensive first-pass metabolism. The aim of this study was to develop QF microemulsion formulation to enhance the bioavailability and to accomplish the intranasal delivery of the drug to the brain. Mucoadhesive in situ gelling systems of QF were formulated to increase the residence time of dosage form and provide sustained release of the drug. Methods Quetiapine fumarate microemulsion (QFME) was prepared using Peceol as oil, Tween 20 as surfactant and Transcutol P as cosurfactant by titration method. Mucoadhesive in situ gelling system of QF was prepared using Pluronic F 127 and chitosan. Results The optimal mucoadhesive microemulsion formulation consisted of 10 % Peceol (glycerol monooleates), 50 % Tween 20/Transcutol P (4:1), 40 % water, 0.3 % Pluronic F127 and 0.2 % chitosan with a maximum solubility of QF up to 42.5 mg/ml, globule size of 148.80 +/- 1.30 nm, zeta potential 32.5 +/- 0.51 and no ciliotoxicity. According to the results of an in vivo pharmacokinetic study in rats, intranasal administration of QF-loaded mucoadhesive microemulsion had a shorter T (max) value (2 min) compared with oral administration and improved bioavailability (89.54 %) compared with oral and intranasal (solution) administration. Conclusion Quetiapine fumarate mucoadhesive microemulsion (QFMME) was successfully formulated as an in situ gelling system which can increase the retention time of the formulation and enhance brain delivery of drugs with improved bioavailability.