In vitro evaluation of ethyl cellulose and polyvinyl pyrrolidone composite nanofibers for transdermal delivery of diclofenac diethylamine

Abstract

Non-steroidal anti-inflammatory drugs (NSAIDs) are the most prominent painkiller and anti-inflammatory drugs with gastrointestinal (GI) adverse effects. Transdermal drug delivery systems (TDDS) could overcome GI adverse effects associated with oral ingestion of NSAIDs as well as maintaining a prolonged release of the drug. The main aim of this study was to prepare and investigate diclofenac diethylamine (DDA) loaded nanofibers made of ethyl cellulose (EC) and polyvinyl pyrrolidone K90 (PVP) using electrospinning. The impact of penetration enhancers such as nerolidol and farnesol on release profiles through cellophane membranes and other characteristics of nanofibers were also investigated. Based on release studies, some formulations were selected for release examination through rate skin using Franz diffusion cells. To gain insight about potential interactions between drug and polymers FTIR, DSC, and XRD analyses were performed. Morphology examination was also conducted using scanning electron microscopy (SEM). Morphology studies showed that nanofibers made of EC only are greater in the mean diameter than other nanofibers while other formulations were not significantly different from each other regardless of the presence of penetration enhancers. EC nanofibers had the lowest elastic modulus and tensile strength and most elongation at break which makes them the least tough and most flexible nanofibers among all the formulations. The addition of PVP increased the toughness and decreased the flexibility of nanofibers. The addition of nerolidol did not alter the mechanical properties of nanofibers significantly, while the addition of farnesol increased elastic modulus, tensile strength, and elongation at break significantly in a concentration-dependent manner. EC nanofibers had the lowest release rate and lowest total cumulative release content while the addition of PVP significantly improved both of these features. In release studies through cellophane membrane, the addition of 5 % of penetration enhancer slightly increased the release rate while did not significantly alter cumulative release while the addition of 10 % farnesol notably increased the release rate and total cumulative released content. Release studies through rat skin were in accordance with cellophane membrane studies and the formulation with 10 % farnesol had the most release rate and total cumulative release and these findings confirm the positive effect of penetration enhancers. DSC thermogram showed an amorphous state of the drug in fibres and this was supported by XRD results. The FTIR results confirmed that no chemical interaction between the drug and other formulation components has occurred and no new compounds have been formed. Based on these results, the utilization of DDA-loaded PVP and EC nanofibers in conjunction with a penetration enhancer showed significant potential for application in transdermal patches.