Abstract
This study aimed to develop and optimize a centrifugally spun polycaprolactone/poly(vinyl alcohol) (PCL/PVA) nanofibrous transdermal patch containing polyethylene glycol 400 (PEG 400) and oleic acid to improve rivastigmine delivery for the long-term management of Alzheimer's disease. Rivastigmine-loaded nanofibrous patches were fabricated by centrifugal spinning and characterized using scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR). Mechanical properties, drug release, ex vivo skin permeation and deposition, dermal irritation, pharmacokinetics in New Zealand White rabbits, and stability were systematically evaluated. The optimized formulation (F5) produced uniform, bead-free nanofibers (1.7 ± 0.3 μm) with rivastigmine molecularly dispersed in an amorphous state within the polymeric matrix. The patch exhibited favorable mechanical properties, sustained drug release, enhanced ex vivo skin permeation (0.50 ± 0.04 mg/cm2 at 24 h), and increased drug deposition within the viable epidermis and dermis, indicating cutaneous reservoir formation. Dermal irritation was negligible (Primary Irritation Index = 0.08). Pharmacokinetic studies demonstrated prolonged systemic absorption (Tmax = 6.0 ± 1.0 h) and approximately five-fold greater systemic exposure (AUC0-∞ = 345 ± 28 ng·h/mL) than the oral formulation (67 ± 9 ng·h/mL, p < 0.05).The optimized centrifugally spun nanofibrous patch provided sustained rivastigmine delivery, excellent dermal biocompatibility, enhanced skin deposition, and improved systemic bioavailability, supporting its potential as a scalable transdermal platform for long-term Alzheimer's disease therapy.