Enhanced systemic delivery of mirtazapine through transdermal drug-in-adhesive matrix: A sustained-release approach

Depression is a prevalent mental health disorder, often associated with systemic side effects, low bioavailability, and poor patient compliance due to conventional oral antidepressants. This study develops and optimizes a transdermal drug-in-adhesive (DIA) matrix patch for Mirtazapine (MTZ), utilizing a pressure-sensitive adhesive (PSA) system and oleic acid as a permeation enhancer. A two-factor, three-level factorial design optimized drug content and flux, yielding 93.09 % drug content and a flux of 56 mg/cm²/h. Preformulation studies confirmed the crystalline nature and excipient compatibility of MTZ. Ex vivo and in vivo evaluations demonstrated enhanced skin permeation, sustained drug release, and improved pharmacokinetics, with a prolonged Tmax of 9 hours and an AUC₀₋ₜ of 7778.85 ng/mL·h, significantly outperforming oral and intravenous routes. Skin irritation studies confirmed formulation safety. This novel transdermal patch presents a promising alternative to oral MTZ, offering controlled systemic drug delivery, improved therapeutic efficacy, and enhanced patient compliance. Future clinical investigations will further validate its potential in depression management.