Journal des médicaments en développement
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Brain Targeting of Duloxetine Nanoemulsion: In vivo Pharmacokinetic and Bio-distribution Studies

Gurpreet Singh, Navleen Kaur Sidhu, Garima Khanna, Amita Sarwal*, Anurag Kuhad

Duloxetine is a potent dual reuptake inhibitor of serotonin and norepinephrine receptors. Due to extensive first- pass metabolism, it has a major limitation of low and variable oral bioavailability. The present study aimed to develop a kinetically stable nanoemulsion using oil, surfactant, and co-surfactant for the better management of the major depressive disorder. The nanoemulsion was prepared by an aqueous titration method. The developed formulation was evaluated for pH, globule size, Transmission Electron Microscopy (TEM), iscosity, transmittance and further it was investigated for in vivo pharmacokinetic and bio-distribution study. According to the results of in vivo pharmacokinetic study in wistar rats, intranasal administration of duloxetine nanoemulsion in the brain had shorter T_max compared with that of intravenous administration. The brain/blood ratios of duloxetine intranasal nanoemulsion, duloxetine intranasal solution, and duloxetine intravenous solution were 4.42 ± 0.09, 2.18 ± 0.14 and 0.19 ± 0.002 respectively. The higher drug targeting efficiency (381%) and direct transport percentage (73.7%) of duloxetine intranasal nanoemulsion as compared to other formulations indicate its better efficacy in the brain. In order to investigate the localization of duloxetine emulsion in brain confocal laser scanning microscopy was carried out using Rhodamine-123 (ROD-123) as a marker.