The Development of a Multilayer Transdermal Patch Platform Based on Electrospun Nanofibers for the Delivery of Caffeine.

: The work presented herein focused on the development and characterization of a transdermal caffeine platform fabricated from ultrathin micro- and submicron fibers produced via electrospinning. : The formulations incorporated caffeine encapsulated in a polyethylene oxide (PEO) matrix, combined with various permeation enhancers. A backing layer made of annealed electrospun polycaprolactone (PCL) facilitated the lamination of the two layers to form the final multilayer patch. Comprehensive characterization was conducted, utilizing scanning electron microscopy (SEM) to assess the fiber morphology, attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) for chemical detection and to assess the stability of the caffeine, and differential scanning calorimetry (DSC) along with wide-angle X-ray scattering (WAXS) to analyze the physical state of the caffeine within the fibers of the active layer. Additionally, Franz cell permeation studies were performed using both synthetic membranes (Strat-M) and ex vivo human stratum corneum (SC) to evaluate and model the permeation kinetics. These experiments demonstrated the significant role of enhancers in modulating the caffeine permeation rates provided by the patch, achieving permeation rates of up to 0.73 mg/cm within 24 h. This work highlights the potential of using electro-hydrodynamic processing technology to develop innovative transdermal delivery systems for drugs, offering a promising strategy for enhancing efficacy and innovative therapeutic direct plasma administration.