鼻腔给药地西泮微乳的制备及性质考察.pdf

64S04Vol.6No.42008M7ChineseJournalofPharmaceuticsJul.2008p.156l20080317Te(1980),o(qB),V3,E-mailchengmei_；(1957),3(qB),a7,q,pV1VY04/,Tel.02423984063,E-mailli_bcI|(2008)04015606080!#I*f(+0Sv0a+110016)K1!iNbZEMm)ZI*aqaVfa#08bT)ZsF8.0%a21.3%Tween80a10.7%PEG400a60.0%bbaib*110-2Pasq12.3mSm-1Vf48.5mNm-131.2nmiO8b!7?08044Gb1oM04Mm08ms|R94DSA(statusepilepticus)BQ30minQ?T?TWuiM*?8Sn$Bb&=Fn0un0b5T01DBDiOKb080=EM?Z&0olya3a8l#PZL+msjbmicroemulsionMEMaMaV4V4a11?Biia*a_OA8B10j100nmWV%aaOa8=yaN51-7bT!080ryaP+iYVMm)Zaqa*VfiX8b1NPSS380；/NPSS.NICOMPParticleSizeSystem,SantaBarbara,USAHFs?N!m0K|0510170Y=?PEG400pKTween80m%KMiglyol812pKbvX830j40gI+0Svi4b2ZET2.1!Miglyol812MY=?PEG400V4Tween804080!#I157V4!b!ZE|)ZMiglyol812aTween80PEG400!c0F)Z25Hq/300rmin-1H20min(HHF)Zbib2.2MmB1|V4V4(V4b191a82a73a64a55a46a37a2819|V4o2.1pHZE!bV4V41sYKm=13a12a11a21a31MmTnm1bL1VUO/WuL2VUW/OuGVU*uEVUYAutf/L1L24usLVUbFig.1Pesudo-ternaryphasediagramsatdifferentKmratiosm1VnKm!1HulKm9Fu9vbyV4?ulKm9FV49v?M9uMvbKm#1HKm9Fu9vOKm=2HuvKm=3Hu=MvbV4V4KD1HV4zO3V49bWKvKvV4?9FV45MhlEv9bWKDKmHV4V4KDrTbNV4&158S046158B8hbyNMiglyol812Tween80PEG4008V4V4KD1Km=2b2.3K)ZYVyI8Miglyol812Tween80PEG400Km=2bcvV4V4PO08*83V4h?h98l-4/hV4V4byN4u=V4180207030H5)Zm2UiBK)Zb)ZnV1bm(Tween80)m(PEG400)=12；Notethatthedilutionline82(solidline)and73(dashedline)aredrawn；iSamplescharacterizedFig.2Pseudo-ternaryphasediagramofMiglyol812,Tween80-PEG400andwatersystemTable1CompositionoftheselectedmicroemulsionformulationsFormulationwMiglyol812/%wTween80/%wPEG400/%wwater/%ME111.129.614.844.4ME28.021.310.760.0ME34.010.75.380.0ME414.622.811.451.2ME69.72.4sY/ZEME1aME2aME3aME4ME5*aqaVfTnV2bNDJ8S3AUT*9*b251Hq/|Av7cm41|060rmin-1b|0A8ASAM7*920j30s*bDDS11CNDJS1sqe250.5b4080!#I159KvE8Vf25b；E4sHqo:633nm:25；_:90o8bTable2PhysicochemicalparametersofthetestedmicroemulsionsMicroemulsionm(S-CoS)m(Oil)d(dropletsize)/nm(solubility)(gL-1)(conductivity)/(mSm-1)/(Pas)(surfacetension)/(mNm-1)ME18:259.69.811.20.18144.5ME28:231.223.312.30.01048.5ME38:244.911.511.20.00352.5ME47:347.812.613.50.02642.8ME57:348.316.911.00.00249.1V2V5)ZME2Kl31.2nmO0Kv23.3gL-1ME1Kv59.6nmyME1)*uuH)ZM1cM?slH*91v0.181Pasb5qvy98MO/WM?A9viO(VfiV0*7$lb080+T4Kv0OKlME2K)Ziv)Z|BMiglyol812aTween80PEG400Fao2.1pHZE!c0iX8b2.5X8IX8Y|X%,f7g8mgsi|/3mm3mm*3!v#*_j*VF0.2mLj400A/4*8fFPibNaHW|SA/48?5b8T:cV07S8THW9bL3|v8s1%)vN080A(X1b2.5.1sk0A8HWsYsk0A08HWTISN4bTnV3bTable3Ciliarybeatdurationevaluatedwithtoadpalatemucosaciliamodelinvitro(n=5)Solutiont(ciliarybeatduration)/minSaline48043Microemulsionofdiazepam450501%Sodiumdeoxycholate183160S0461602.5.2sk0A84T3A4sk0A8ivTnm3bABCFig.3Morphologyoftheciliaunderopticalmicroscopeafteradministrationofnegativecontrol(A)(saline,ciliaonthemucosakeptintact,denseandbeatactively8haftertreatment),microemulsionofdiazepam(B)(similarphenomenonwiththatofsalinevisualized8haftertreatment),positivecontrol(C)(1%sodiumdeoxycholate,nociliaonthemucosaobservedbutafewexfoliatedcilia30minaftertreatment)TV38*VbVnO?p_BZ_qHW(48043)minbME2j7b8AyGHW8vM7H8GEsbEs(45050)min8Tb0*BTYv8lb)A/Esybj7S=Es88XV)*FT8VITb3)a.LMiglyol812MTween80V4PEG400V4bMiglyol812iOza(zbTween80cYd0V4HLB15.0!O/W1pOl?bV4V0Vf9vTlO3MzPEG400V4bb.!VMm)ZMiglyol812Tween80PEG4008V4V41Km=2HMKDrTbN$5)Z#0IKK)Zbc.08*VBLVsv*Ai8bf/8xBb08=sb8s%)hH8*AssY$%hb080n5s80#0*#8(TY083?10byN0804HI40*F081bT8HWZEN0408TVME28lb4080!#I161ID1VYASTK,BABBARAK,SHARMARK,etal.Intranasalmucoadhesivemicroemulsionsofclonazepam:preliminarystudiesonbraintargetingJ.JournalofPharmaceuticalSciences,2006,95:570580.2LIANLL,SUDHIRG,YONGMC,etal.Rapid-onsetintranasaldeliveryofanticonvulsants:pharmacokineticandpharmacodynamicevaluationinrabbitsJ.IntJournalofPharmaceutics,2000,199:6576.3AMMONCS,SHAFIRB.Transdermaldrugdeliveryusingmicroemulsionandaqueoussystems:InfluenceofskinstorageconditionsontheinvitropermeabilityofdiclofenacfromaqueousvehiclesystemsJ.IntJournalofPharmaceutics,2006,311:5562.4LINDHARDTK,OLAFSSONDR,GIZURARSON,etal.IntranasalbioavailabilityofdiazepaminsheepcorrelatedtorabbitandmanJ.IntJournalofPharmaceutics,2002,231:6772.5=Z,fl.n04#+J.B+Dv,2001,21(12):8083.6X,.yIJ.+0Sv,2005,22(2):9699.7f,S.080d0T#%oJ.SD0,2001,32(7):323327.8*.；Essdp,4vlsJ.+0Sv,2003,20(5):336338.9GAOXL,TAOWX,LUW,etal.Lectin-conjugatedPEGPLAnanoparticles:PreparationandbraindeliveryafterintranasaladministrationJ.Biomatericals,2006,27:34823490.10A.0*ZJ.0,2005,20(2):8889.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,12.3mSm-1,48.5mNm-1and31.2nm,respectively.Thediazepammicroem