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 英国SMSTA.XTPlus质构仪(TA.XTPlus物性测试仪)