鼻腔给药地西泮微乳的制备及性质考察

64Vol.6No.420087ChineseJournalofPharmaceuticsJul.2008p.15620080317(1980–),(),,,[e-mail];(1957–),(),,,,Tel.[phone],[e-mail](2008)04–0156–06(110016)8.0%21.3%Tween8010.7%PEG40060.0%110-2Pa·s12.3mS·m-148.5mN·m-131.2nmR94A(statusepilepticus)30minmicroemulsionME10100nm[1-7]1PSS380/PSS.NICOMPParticleSizeSystem,SantaBarbara,USA0510170PEG400Tween80Miglyol8123040g22.1Miglyol812PEG400Tween804157Miglyol812Tween80PEG40025300r·min-120min2.29182736455463728192.1Km=13121121311L1O/WL2W/OGEL1L2LFig.1Pesudo-ternaryphasediagramsatdifferentKmratios1Km1KmKmKm1KmKm=2Km=3Km1586158Miglyol812Tween80PEG400Km=22.3Miglyol812Tween80PEG400Km=280207030521m(Tween80)m(PEG400)=12;Notethatthedilutionline82(solidline)and73(dashedline)aredrawn;●SamplescharacterizedFig.2Pseudo-ternaryphasediagramofMiglyol812,Tween80-PEG400andwatersystemTable1CompositionoftheselectedmicroemulsionformulationsFormulationwMiglyol812/%wTween80/%wPEG400/%wwater/%ME111.129.614.844.4ME28.021.310.760.0ME34.010.75.380.0ME414.622.811.451.2ME59.114.17.169.72.4ME1ME2ME3ME4ME52NDJ8S25±17cm160r·min-12030sηDDS11CDJS125±0.5415925:633nm:25:90o[8]Table2PhysicochemicalparametersofthetestedmicroemulsionsMicroemulsionm(S-CoS)m(Oil)d(dropletsize)/nmρ(solubility)(g·L-1)σ(conductivity)/(mS·m-1)η/(Pa·s)γ(surfacetension)/(mN·m-1)ME18:259.69.811.20.18144.5ME28:231.223.312.30.01048.5ME38:244.911.511.20.00352.5ME47:347.812.613.50.02642.8ME57:348.316.911.00.00249.125ME231.2nm23.3g·L-1ME159.6nmME10.181Pa·s5O/WME2Miglyol812Tween80PEG4002.12.53mm×3mm0.2mL400[9]1%2.5.13Table3Ciliarybeatdurationevaluatedwithtoadpalatemucosaciliamodelinvitro(n=5)Solutiont(ciliarybeatduration)/minSaline480±43Microemulsionofdiazepam450±501%Sodiumdeoxycholate18±316061602.5.23ABCFig.3Morphologyoftheciliaunderopticalmicroscopeafteradministrationofnegativecontrol(A)(saline,ciliaonthemucosakeptintact,denseandbeatactively8haftertreatment),microemulsionofdiazepam(B)(similarphenomenonwiththatofsalinevisualized8haftertreatment),positivecontrol(C)(1%sodiumdeoxycholate,nociliaonthemucosaobservedbutafewexfoliatedcilia30minaftertreatment)(480±43)minME2(450±50)min3a.Miglyol812Tween80PEG400Miglyol812Tween80HLB15.0O/WPEG400b.Miglyol812Tween80PEG400Km=25c.[10]ME24161[1]VYASTK,BABBARAK,SHARMARK,etal.Intranasalmucoadhesivemicroemulsionsofclonazepam:preliminarystudiesonbraintargeting[J].JournalofPharmaceuticalSciences,2006,95:570–580.[2]LIANLL,SUDHIRG,YONGMC,etal.Rapid-onsetintranasaldeliveryofanticonvulsants:pharmacokineticandpharmacodynamicevaluationinrabbits[J].IntJournalofPharmaceutics,2000,199:65–76.[3]AMMONCS,SHAFIRB.Transdermaldrugdeliveryusingmicroemulsionandaqueoussystems:Influenceofskinstorageconditionsontheinvitropermeabilityofdiclofenacfromaqueousvehiclesystems[J].IntJournalofPharmaceutics,2006,311:55–62.[4]LINDHARDTK,OLAFSSONDR,GIZURARSON,etal.Intranasalbioavailabilityofdiazepaminsheepcorrelatedtorabbitandman[J].IntJournalofPharmaceutics,2002,231:67–72.[5],.[J].,2001,21(12):80–83.[6],,,.[J].,2005,22(2):96–99.[7],.[J].,2001,32(7):323–327.[8].[J].,2003,20(5):336–338.[9]GAOXL,TAOWX,LUW,etal.Lectin-conjugatedPEGPLAnanoparticles:Preparationandbraindeliveryafterintranasaladministration[J].Biomatericals,2006,27:3482–3490.[10].[J].,2005,20(2):88–89.PreparationandevaluationofdiazepammicroemulsionforintranasaldeliveryJIAOCheng-mei,LIUHong-zhuo,JINGLing-yu,ZHANGYu,LISan-ming(Schoolofpharmacy,ShenyangPharmaceuticalUniversity,Shenyang110016,China)Abstract:ObjectiveTopreparediazepammicroemulsionandevaluateitsquality.MethodsTheformulationofdiazepammicroemulsionwasselectedusingpseudoternaryphasediagram.Theviscosity,conductivity,surfacetension,dropletsizeandnasalciliotoxicityofthemicroemulsionwerecharacterized.ResultsThemicroemulsionwascomposedofMiglyol812(8.0%),Tween80(21.3%),PEG400(10.7%)andwater(60.0%),anditsviscosity,conductivity,surfacetensionanddropletsizewere0.010Pas,12.3mS·m-1,48.5mN·m-1and31.2nm,respectively.Thediazepammicroemulsionhadonlyslightnasalciliotoxicity.ConclusionDiazepammicroemulsioncouldbepreparedusingMiglyol812-Tween80-PEG400-watersystem,whichcanbeusedforintranasaladministration.Keywords:pharmaceutics;microemulsion;pseudo-ternaryphasediagram;diazepam;nasalciliotoxicity