Duloxetine loaded-microemulsion system to improve behavioral activities by upregulating serotonin and norepinephrine in brain for the treatment of depression

Duloxetine is a well-known antidepressant molecule which is used in the treatment of depression but due to poor solubility it suffers with the drawback of low oral bioavailability. The objective of present work was to formulate and characterize duloxetine loaded microemulsion to enhance the oral bioavailability. Prepared microemulsion was studied for droplet size, zeta potential, refractive index, polydispersity index (PDI), percentage transmittance, viscosity and in vitro release study. Optimized microemulsion (D1) showed spherical droplets with mean diameter of 35.40 ± 3.11 nm, PDI of 0.170 and zeta potential values of −25.8 mV. Formulation showed good transmittance (greater than 99%), viscosity (0.205 Pa s) and refractive index (1.43 ± 0.01). Increased duloxetine release was obtained with microemulsion in comparison to drug suspension. Behavioral tests like mobility test, tail suspension test and forced swimming test performed in depressed and treated rats with duloxetine microemulsion significantly improved the behavioral activities in comparison to duloxetine suspension. Pharmacokinetic studies showed that microemulsion exhibited 1.8 times increment in bioavailability in comparison to duloxetine suspension.