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Quetiapine Fumarate Loaded Mucoadhesive Nanoemulsion: Formulation, Optimization & Brain Delivery via Intranasal Administration

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Background and Objectives: The aim of present study was to prepare quetiapine fumarate (QF) loaded NE and mucoadhesive NE to enhance the uptake of QF to brain via intranasal (i.n.) delivery.

Method: On the basis of solubility studies capmul MCM was selected as the oily phase. The NE was optimized using response surface methodology. A numerical optimization technique was employed to determine the optimal values of variables using desirability approach. Effect of independent variables [(Smix water ratio (X1), stirring speed (X2) and stirring time (X3)] on the dependent variables globule size (Y1) and in vitro drug release (Y2) was statistically optimized using 23 full factorial design. The optimized batch of NE and mucoadhesive NE was further characterized and evaluated by morphology, zeta sizer, zeta potential, viscosity, pH, transmittance, conductivity, drug content, in vitro release kinetics, ex-vivo permeation and in vivo biodistributionstudies. In order to investigate the localization of QF in brain and nose, qualitatively confocal laser scanning microscopy technique was carried out using coumarin-6 as a marker.

Results: Globule size of formulation was antagonistically effected by the independendent variables, whereas the effect was synergistic on the in vitro drug release. The optimal calculated parameters were found to be Smix water ratio (60:25), stirring speed (1000 rpm) and stirring time (15 min).

Conclusion: The results of the present investigation showed that QF can be given through intranasal route. This leads to increase in therapeutic effect with lower dose and reducing the side effects by decreasing the drug concentration in other organs. The formulation was free from nasal ciliotoxicity and a more than 14 folds increase in relative bioavailability of QF as compared to oral NE suggested that formulation provides a better mode of systemic delivery of QF.
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Keywords: Brain targeting; biodistribution; blood-brain-barrier; brain delivery; nanoemulsion; optimization

Document Type: Research Article

Publication date: May 1, 2016

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  • Drug Delivery Letters publishes short papers in all important aspects of drug delivery, gene delivery, and drug targeting. Short papers report seminal results and research approaching conclusion of importance in the field.

    The journal scope covers all basic and applied research in drug delivery and targeting at molecular and cellular levels and novel delivery systems. The manuscript submission process is fully electronic , to ensure the rapid publication of research results.

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