Design and optimization of venlafaxine niosomes loaded thermosensitive in-situ gel for prolonging intranasal residence in depressive disorder.

Abstract

Objective: Venlafaxine (VLF) is the most commonly used drug for the treatment of depressive disorder. The oral bioavailability of VLF is low. Therefore, the present study emphasized the development of niosomes formulation for solubility and permeation improvement.

Methods: The niosome-VLF was formulated using a thin film hydration technique employing different molar ratios of Span 40 and cholesterol. The optimization of niosomes was performed using the Box-Behnken screening model, which employs numerical optimization.

Results: The optimized niosmoes-VLF showed Particle size: 264.2 ± 2.2 nm; Zeta potential: 49.2 ± 1.3 mV; Polydispersity Index: 0.265 ± 0.15; Entrapment efficiency: 70.25 ± 1.5%. The niosome-VLF (OF) was incorporated into the thermosensitive in situ gel (TISG). The niosome-VLF TISG (OF-A) showed gelling temperature: 37 ± 0.5 °C; gelling time: 23 ± 2.2 s; viscosity: 4526 ± 142 cps; mucoadhesive strength: 3589 ± 65 dyne/cm², drug content: 88 ± 5.4%. The in-vivo pharmacokinetic study revealed a higher concentration of VLF in developed niosome-VLF TISG (OF-A) formulation than VLF suspension. The higher and sustained concentration of VLF in brain and plasma suggested a better therapeutic approach to counteract a chronic depressive disorder. Further, the accelerated stability studies of niosome-VLF TISG (OF-A) indicated good physical and chemical attributes.

Conclusion: The intranasal niosome-VLF TISG (OF-A) can be sorted as an alternative approach for targeting the brain for the effective management of CNS conditions like depression.