Preparation and characterization of diclofenac transdermal patch using ethyl cellulose and polyvinyl alcohol by electrospinning

Abstract

In recent years, the adverse effects linked to the oral administration of diclofenac, a non-steroidal anti-inflammatory drug (NSAID), have urged interest in exploring alternative administration routes, specifically transdermal drug delivery (TDD). Among the techniques emerging for creating nanoscale fibres suitable for TDD systems, electrospinning has attracted attention. The primary objective of this study was to formulate and evaluate nanofibers loaded with diclofenac diethylamine using ethylcellulose (EC) and polyvinyl alcohol (PVA) polymers. The influence of penetration enhancers, namely farnesol and nerolidol, on the properties of these fibres was investigated. Employing the electrospinning technique, nanofibers composed of EC or PVA polymers, with or without penetration enhancers, were fabricated, all maintaining a constant drug-to-polymer ratio. Mechanical strength and release kinetics from a cellophane membrane for the obtained nanofibers were investigated. A Franz diffusion cell was employed to determine the drug penetration rates through rat skin for selected fibre formulations. To gain insights into potential interactions and changes in the drug's solid state, FTIR spectroscopy, DSC, and XRD analyses were conducted. Microscopic examination unveiled that EC-based fibres exhibited homogeneity and lacked bead formations, albeit with larger diameters than other formulations. In contrast, both EC and PVA-based fibres displayed bead formations and nanometer-scale widths. The incorporation of penetration enhancers led to the production of uniform, bead-free nanofibers, with minor impacts on fiber size. EC fibres exhibited the lowest tensile strength and modulus of elasticity, but maximum flexibility. The addition of PVA and penetration enhancers contributed to enhanced fibre toughness and resistance to deformation. These alterations also positively influenced drug release rates, as observed in experiments conducted on cellophane membranes. Notably, when comparing drug release on rat skin to cellophane membranes, a slower initial release followed by a steeper slope was noted, attributed to the beneficial role of penetration enhancers on skin permeation. Analyzing results from DSC revealed the transition of the crystalline form of diclofenac diethylamine to an amorphous state within the nanofiber matrix which was also supported by XRD data. In light of these findings, electrospun nanofibers comprising a combination of EC and PVA polymers, alongside a penetration enhancer and diclofenac diethylamine, exhibit considerable promise for utilization as transdermal patches.