Development and in vitro evaluation of estradiol transdermal film-forming spray

To develop estradiol transdermal film-forming spray (TFS), various polymers were screened using solvent appearance, spray ability, film-forming rate and appearance as indices.  The influence of polymer type, plasticizer and penetration enhancer on the transdermal flux were investigated by selecting porcine skin as model, and transdermal flux of TFS was compared with commercial patch and gel.  The drug existing state in the formed film was investigated by differential scanning calorimetry (DSC).  The solvent appearances, spray abilities, film-forming rates and appearances of eudragit E PO, RL PO, hydroxypropyl cellulose EF, polyvinylpyrrolidone K30, Plasdone S630 and Agrimer VA64 were suitable for the preparation of TFS.  TFS prepared by Eudragit RL PO had the biggest transdermal flux of estradiol among all the polymers investigated.  Triethyl citrate, the plasticizer, decreased the transdermal flux.  Azone increased the transdermal flux, while oleic acid, isopropyl myristate and menthol had opposite effects.  TFS had a higher transdermal rate and a higher accumulative penetrated estradiol of 24 h than commercial patch and gel.  The DSC result showed that estradiol was spread as molecule in the formed film of TFS.  It was indicated that TFS could be expected to be an effective transdermal drug delivery system.