Non-invasive intranasal delivery of quetiapine fumarate loaded microemulsion for brain targeting: Formulation, physicochemical and pharmacokinetic consideration

摘要: Systemic drug delivery in schizophrenia is a major challenge due to presence of obstacles like, blood-brain barrier and P-glycoprotein, which prohibit entry drugs into the brain. Quetiapine fumarate (QF), substrate P-glycoprotein under goes extensive first pass metabolism leading limited absorption thus necessitating frequent oral administration. The aim this study was develop QF based microemulsion (ME) with without chitosan (CH) investigate its potential use improving bioavailability brain targeting efficiency following non-invasive intranasal loaded ME mucoadhesive (MME) showed globule size, pH viscosity range 29-47nm, 5.5-6.5 17-40cP respectively. CH-ME spherical globules having mean size 35.31±1.71nm, value 5.61±0.16 highest ex-vivo nasal diffusion (78.26±3.29%) 8h no sign structural damage upon histopathological examination. Circular plume an ovality ratio closer 1.3 for depicted ideal spray pattern. Significantly higher brain/blood comparison QF-ME solution administration revealed prolonged retention at site action suggesting superiority CH as permeability enhancer. Following administration, 2.7 3.8 folds compared respectively indicative preferential nose transport (80.51±6.46%) bypassing barrier. Overall, above finding shows promising results area developing route alternative delivery.