Nanotechnology-Driven Transdermal System for Loxapine Succinate: A Novel Strategy To Improve Pharmacokinetics and Therapeutics in Psychotic Disorders

Abstract

Loxapine succinate, an antipsychotic agent with limited oral bioavailability (30%) due to extensive Hepatic first-pass metabolism, demands innovative delivery strategies to enhance therapeutic efficacy. This study presents a novel transdermal Drug delivery system incorporating loxapine succinate-loaded chitosan nanoparticles designed to overcome these limitations. The nanoparticles, synthesized via ionic gelation, exhibited an optimized average diameter of 261.5 nm, a polydispersity index (PDI) of 0.498, and a Drug entrapment efficiency of 49.5%. These nanoparticles were integrated into pressure-sensitive adhesive (PSA) transdermal patches to facilitate sustained drug release and improved skin adhesion. Characterization studies using Fourier-transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), and X-ray diffraction (XRD) confirmed structural compatibility and stability. In vitro Drug release studies demonstrated a progressive diffusion profile, while ex vivo permeation studies using porcine skin achieved a cumulative Drug permeation of 59.52% over 72 h, enhanced by the inclusion of 0.5% w/v limonene as a permeation enhancer. Pharmacokinetic assessments in Wistar rats revealed a sustained plasma concentration of 1540.76 ng/mL for 72 h using a 50 cm² patch, corresponding to a 3.99-fold and 5.2-fold increase in bioavailability compared to intravenous and oral administration, respectively. This nanoparticle-integrated transdermal platform effectively addresses key challenges in loxapine delivery by improving bioavailability, reducing dosing frequency, and promoting patient adherence in the management of psychotic disorders. The findings underscore the potential of nanotechnology-enhanced transdermal systems for advancing therapeutic outcomes in chronic psychiatric conditions.