Development and in vitro evaluation of mucoadhesive gelatin films for the vaginal delivery of econazole

Several strategies have been explored to obtain effective econazole nitrate (ECN) concentrations at the site of application for a prolonged time. In this paper, different gelatin-based film formulations for vaginal application were investigated, containing ECN (10% w/w with respect to gelatin) as pure drug or as drug-solid dispersions (SD). For the production of SD, different polymers were evaluated: polyvinylpyrrolidone (PVP), Soluplus® (polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer) and Gelucire® 50/13 (mixture of mono-, di- and triglycerides of fatty acids, esters of PEG 1500 and free PEG). Gelucire® -SD showed the best solubility enhancement, increasing 9.2 times the ECN solubility in pH 4.5 solution respect to pure drug; DSC and XRD analysis confirmed the crystalline form of the drug. XRD results evidenced that all gelatin-based films, containing either the drug or the SD, underwent the topotactic transformation of ECN into crystalline econazole (EC), owing to a strong interaction between the drug and the gelatin. Films containing Gelucire®-based SD displayed lower brittleness and rigidity with respect to the other samples; moreover they demonstrated good structural integrity after 24 h of incubation in the acidic solution (swelling degree of about 350%). Then, Gelucire®-SD based films were compared with the corresponding formulations cross-linked by genipin (2% w/w). The addition of genipin did not interfere with the drug-gelatin interaction. Gelucire®-SD based films showed similar release profiles to neat gelatin films, enhancing the drug release in the first 5 h and controlling the EC release over time, avoiding the use of a crosslinking additive. Finally, gelatin films containing Gelucire® solid dispersion displayed good adhesiveness and anti-Candida activity. Overall, results support the potential use of this film formulation as noncytotoxic EC delivery system for the treatment of vaginal candidiasis. Continue on mucoadhesive gelatin films for the vaginal delivery of econazole

Keywords Econazole, Solid dispersion, Solubility, Gelatin films, Solvent casting, Vaginal delivery, Controlled release

Chemical compounds studied in this article
Econazole nitrate (pubChem CID: 68589), Type A gelatin, Soluplus® (polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer: PCL-PVAc-PEG), Kollidon®30 (polyvinylpyrrolidone), Kollidon®VA64 (polyvinylpyrrolidone-vinyl acetate), Gelucire® 50/13 (a mixture of mono-, di- and triglycerides, mainly mono- and diesters of palmitic (C16) and stearic (C18) acids), esters of PEG 1500 and also free PEG), Genipin