Design of novel miconazole nitrate transdermal films based on Eudragit RS100 and HPMC hybrids: preparation, physical characterization, in vitro and ex vivo studies

摘要

The objective of this study was to formulate and evaluate transdermal films containing miconazole nitrate (MN), a poorly water-soluble imidazole antifungal agent, with a view to enhancing its delivery across intact skin. Transdermal films of MN were formulated by solvent casting technique using admixtures of film-forming polymers – Eudragit RS100 and hydroxypropylmethylcellulose (HPMC) (2:8, 4:6, 5:5, 6:4 and 8:2) with polyethylene glycol 8000 (plasticizer and permeation enhancer) and Tween 80 (mobile surfactant). The films were evaluated for weight uniformity, folding endurance, thickness, moisture loss and uptake, bioadhesive strength, drug content, skin irritation on rabbits and time-resolved stability. The ex vivo release of MN from the films was carried out using a modified Franz diffusion apparatus while the microbiological evaluation was conducted using a clinical isolate of Candida albicans. Overall results indicate that films made with two portions of Eudragit RS100 and eight portions of HPMC (batch T-1) had the least weight variation (57.33?±?0.27?mg), folding endurance (307.90?±?4.17), moisture uptake (1.37?±?0.28%) and thickness (145.9?±?2.08?μm), but highest drug content (97.50?±?2.43%) and bioadhesive strength (81.40?±?2.03?dyne/cm2), best bioactivity and in vitro skin permeation through rat skin with highest permeation flux (5.161?μg/cm2?h) and permeation coefficient (1.032?×?10?6?cm/h) compared to all other formulations. This study has established that transdermal films based on 2:8 admixtures of Eudragit RS100 and HPMC could offer a promising approach for the treatment of skin infections caused by MN-susceptible fungi.