Characterization of hot-melt extruded dr

Abstract Theobjectivesofthisinvestigationweretostudythephysico-chemicalpropertiesofhot-meltextruded(HME)lmsforonychomycosisandtodeterminethestabilityofthemodelantifungaldrugincorporatedwithintheselms.Theinuenceofetchingandinstrument variablesonthebioadhesionofthesedrugdeliverysystemsforthehumannailwasalsostudied.Six250gbatches(F1CF6ofhydroxy propylcellulose(HPC)and/orpoly(ethyleneoxide)lmscontainingketoconazole(20%)wereextrudedusingaKillionextruder(Model KLB100).ThethermalpropertiesofHMElmswereinvestigatedusingdierentialscanningcalorimetry(DSC).Scanningelectron microscopy(SEM)wasusedtoexaminethesurfacemorphologyofthelmsandX-raydiraction(XRD)wasusedtoinvestigatethe crystallinepropertiesofthedrugs,physicalmixturesaswellastheHMElms.Stabilitystudieswereperformedonthelmsstored at25C/60%RH.Thebioadhesivepropertiesoftheselmswereinvestigatedonthehumannail(exvivo)usingaTextureAnalyzer . Thenailsamplestestedwereeithernon-treated(control)ortreatedwithanetchinggel.Theparametersmeasuredwerepeakadhesion force(PAF)andareaunderthecurve(AUC).TheHansensolubilityparameterwascalculatedusingacombinationofHoyandHofty- zer/VanKrevelenmethodstoestimatethelikelihoodofdrugCpolymermiscibility.SEMprovideddirectphysicalevidenceofthephysica stateofthedrugwithinthelms.Thetheoreticalpost-extrusioncontentofketoconazoleremaininginthesixlmbatchesrangedfrom 90.3%(2.2)to102.4%(9.0)forupto6monthsandfrom83.9%(3.6)to91.6%(3.0)forupto12months.Bioadhesionstudi HPClmtestedonfietchedflnailsrecordedsignicantlyhigherPAFandAUCthanthatofthenon-treatedficontrolflnails.Ketocona wasfoundtoberelativelystableduringtheextrusionprocess.Meltingpointscorrespondingtothecrystallinedrugswerenotobservedin theprocessedlms.TheHansensolubilityparameterspredictedmiscibilitybetweenthepolymersandthedrug.Thepredictionsofthe solubilityparameterswereinagreementwithDSC,XRDandSEMresults.Bioadhesionmeasurementsofthelmonthehumannail substrateweregenerallyhigherfortheetchednailsthanthatofthecontrolnails. 2006ElsevierB.V.Allrightsreserved. Keywords: Nail;Hot-meltextrusion;Stability;Bioadhesion;Textureanalyzer