Preparation, characterization and pharmacokinetic release of diclofenac sodium-dual layer polyvinyl alcohol patch for transdermal delivery

Abstract

Polyvinyl alcohol (PVA) has been broadly used in biomedical applications due to its biocompatibility, non-toxicity, nanofiber and hydrogel-forming ability. Despite these advantages, their structures are easily disrupted due to water absorption (swelling), thus resulting in the burst release of drugs due to drug leaching in transdermal delivery. Therefore, this study mainly aimed to prepare the diclofenac sodium (DS) medicated dual layer PVA patch by a combination of electrospinning and cryogelation (freeze-thaw) methods to reduce the swelling capacity and enhance the physicochemical and mechanical properties with good drug compatibility between the DS and PVA cryogel. Then, to subsequently evaluate the kinetic release mechanism using four different mathematical models. The morphological analysis of the crosssection demonstrates good polymer-polymer interaction between both layers and, fourier transform infrared (FTIR) and x-ray diffraction (XRD) also demonstrate good dispersion and entrapment of DS in the PVA matrix limited to 2% w/v. The DS loads were found to be homogeneously dispersed in the PVA matrix as no visible FTIR spectra of DS-PVA interaction was identified. The crystallinity level of the dual layer PVA patches also increased as the nanofiber thicknesses and freeze-thaw cycles increased. The hydrophilicity of the dual layer PVA patch also decreased, with increases in all other parameters. The DS-medicated dual layer PVA patch labelled as 2%DLB5C shows the lowest percentage of swelling capacity (13.49%). All formulations of the dual layer PVA patch show an enhancement in tensile strength but a decrease in elasticity as the DS percentage loading increases. The 2%DLA5C and 2%DLb5C exhibited good mechanical properties with the highest tensile strength (538.19 and 551.73 KPa, respectively), also a lower percentage of elongation and the highest values of elastic modulus. The Franz-diffusion assessment uncovered that the 2%DLa5C and 2%DLb5C have better sustainable releases of DS (~49% after 12 hours). The 2%DLA5C and 2%DLB5C had a flux (Jss) of 0.220 and 0.231 mg/cm2/h, respectively, and a permeability coefficient (Kp) value of 0.018 cm/h for both patches. The release of DS for both patches follows the Higuchi and Korsmeyer-Peppas models. Based on these findings, a dual layer PVA patch with thicker nanofiber, higher freeze-thaw cycles, and higher DS loading percentages has lowered the swelling capacity yet improved the physicochemical and mechanical properties and is suitable for transdermal patches. In conclusion, both medicated dual layer PVA patches can complete the release of the DS for up to 24 hours with the one-time application, hence would serve as promising transdermal drug delivery.