A Compressive Review on: Transdermal Delivery for Trazodone in Depression and Sleep Disorder

Trazodone, a triazolopyridine antidepressant, is currently available only in oral dosage forms. Delivering this drug through the skin could help minimize adverse effects associated with high peak plasma levels and enhance patient compliance by reducing dosing frequency. This study aimed to assess how vehicle pH and permeation enhancers influence the ex-vivo permeation of trazodone through porcine skin, and design and optimize a transdermal delivery system containing trazodone hydrochloride. The findings indicate that the vehicle pH exerts a complex influence on trazodone skin permeation, as it affects both drug solubility and its partitioning into the skin. Additionally, fatty acids incorporated into the vehicle markedly increased permeation, with an enhancement factor of approximately 100. Transdermal drug delivery systems (TDDS) offer an alternative route for administering trazodone, an antidepressant with serotonin antagonist and reuptake inhibitor (SARI). By bypassing the gastrointestinal tract and first-pass hepatic metabolism, transdermal formulations can reduce systemic side effects, provide controlled and sustained drug release, and enhance therapeutic efficacy, particularly in patients with sleep disturbances or adherence challenges. Challenges in formulating trazodone for transdermal delivery include its molecular size, lipophilicity, and skin permeability. Recent research has explored permeation enhancers, novel polymeric matrices, and Microneedle-assisted delivery to optimize absorption. Overall, transdermal delivery of trazodone represents a promising approach to enhance clinical outcomes while minimizing adverse effects associated with oral administration.