Bioavailability Enhancement of Paroxetine Loaded Self Nanoemulsifying Drug Delivery System (SNEDDS) to Improve Behavioural Activities for the Management of Depression

Paroxetine is a one of well-known anti-depressant but due to extensive hepatic first pass metabolism it suffers with shortcoming of poor oral bioavailability. Aim of current study was to develop and evaluate paroxetine loaded SNEDDS to increase oral bioavailability. SNEDDS were formulated by using caproyl 90 as oil phase, Cremophore EL as surfactant and propylene glycol as co-surfactant. Optimized SNEDDS exhibited spherical globules with diameter of 67.17 nm, PDI of 0.283 and zeta potential values of − 13.7 mV. SNEDDS showed good transmittance (higher than 99%). Enhanced paroxetine release was obtained with SNEDDS. Intestinal permeability studies and everted gut sac studies showed that there was increment in drug permeation in case of paroxetine loaded SNEDDS as compared to suspension. Results of behavioural study revealed that the depressed rats received paroxetine SNEDDS orally improved the behavioural activities in comparison to drug suspension by decreasing depletion of serotonin and norepinephrine therefore assisting in treatment of depression. Pharmacokinetic studies indicated that oral bioavailability of paroxetine SNEDDS increased 2.3 times as compared to paroxetine suspension. Cell line toxicity confirmed no sign of toxicity of developed formulation. In this way, oral paroxetine SNEDDS delivery can play a critical role in improving depression management.