课件汇总-2014物理药学phase and transformation

Phase&PhasetransformationPhaseDefinitionofphaseGasLiquidSolidExamplesinpharmaceuticalresearchdrugabsorptionpolymorphism

StatesofMatter,TheCharacteristicsState FluidityCompressibility__________________________________________________________Gas Yes YesLiquid Yes NoSolid No NoLiquid Yes YesCrystal(2D)Powder YesYesRubber No Yes__________________________________________________________PharmaceuticallyRelevantGasesIdeaGas PV=nRT R=0.082 R=8.314 R=1.987RealGas (P+)(V–nb)=nRT

an2V2 a(L2atm/mol)b(L/mol)H2 0.244 0.027O2 1.360 0.032CH4 2.253 0.043H2O 5.464 0.031Cl2 6.493 0.056a/V2:internalpressure countsattraction betweenmoleculesb: excludedvolume countssizeof moleculesPharmaceuticallyRelevantLiquidsacetonbenzenewaterAceticacid020406080100Pressure/mmHgVaporizationofLiquidsandAerosolsln=P2P1Hv(T2–T1)T1T2Clausius-ClapeyronEquationPharmaceuticallyRelevantSolidsCrystalsNaClCrystalProteinCrystalPharmaceuticallyRelevantSolidsPolymersGlassCrystalGelTemp.SolventRepeatedtreatmentPhaseDiagramTempPressure.SingleComponentMultiComponentGibbsPhaseRuleF=C–P+2FreedomComponentsPhasesABCOPhaseDiagrams,ExamplesEutecticMixture0---------w/w%ofcomponentB---------100TemperatureOneliquidphaseSolidA+liquidSolidB+liquidSolidA+SolidBPhaseDiagrams,ExamplesNicotineinwater0-------w/w%ofNicotine---------10060.8°C208°CTemperaturetwophasesonephasePhaseDiagrams,ExamplesThreecomponents0%ofDextraninwater100%ofPEGinwater100基于水相－水相乳化的蛋白缓释微球制备工艺亲水聚乙二醇连续相聚电解质亲水表面亲水多糖分散相，蛋白靠热力学原理分配其中水相－水相乳液粒径均一的蛋白缓释微球冻干蛋白-多糖颗粒心脏支架表面微球包封镀膜纤维化组织工程纤维freezinglyophilizedemulsifywashedvacuumwashedApproach水相-水相乳化及水相冷冻相分离原理W=1030 W103S=klnW

GM=HM–TSM

++++++++++++++++++++++-V__________-++--++-两相区单相区相图扩散双电层表面距离蛋白-多糖微粒及含有微粒的PLGA微球水相－水相乳化法冷冻相分离法微粒微球Phase-transitionMicroneedles

Workingprinciples:SubcutaneoustissuewithbloodvesselsandnervesEpidermisDermisSwellingfrontmovingupgradualyPenetratingdermalbutnottouchnerve,convertingtogelbyabsorbingbodyfluidGlassystatepriortowaterabsorptionHydrogelstateafterwaterabsorptionDrugloadedhydrogelinglassystateProteinsarekeptinglassymatrixpriortobodyfluidinducedrelease16T.Jin;ConfidentialSwellingbybodyfluidIntegratedsupportingplateInsulinloadingcapacity：5-10mgPhase-transitionMicroneedles50μm0.6mmControlledinsulinreleasebypatchswelling17Workingprinciples:T.Jin;ConfidentialPhase-transitionMicroneedlesABCDPrototypesamplesofthepatch:A:withanickel;B:crosssection;C:drystate;D:swollenafterinsertinghumanskin18T.Jin;ConfidentialPhase-transitionMicroneedlesbeforeneedlepenetrationrightafterneedlepanetration30minafterneedlepenetration90minafterneedlepenetrationPenetrationtolivehumanskin:MicroholesformedBodyfluidmovedupCompleterecovery19T.Jin;ConfidentialBiomoleculesarepartitionedinthermodynamicallyPEGPCLDexPCLPEG-PCLDEX-PCLDextrandispersedphasePEGcontinuousphasePolymersomeofAsymmetricBilayerSubmicronEncapsulationofEPO21ReleaseprofileofEPOfromourpolymersomesofasymmetricbilayermembraneBioactivityofEPOreleasedfromourpolymersomesassayedbyUT-7cellproliferationResults:Encapsulationefficiencyfrom5%upto90%,Activitypreservation≈100%Rationales:Thermodynamicpartition,∆G=-RTlnKP

BiologicalPathwaysforGeneDeliverybySyntheticCarriers22＋+++++++++++++++DNA/RNAPolycationsTargetinggroupPolyplexNucleusEndosomeHClDNA/RNACarrierfragmentsCondensingTargetingEndosomalescapeGenereleaseCarrierdegradeEngulfingABC

DERationallyDesignofNucleotideCarriers

FluvirusMulti-functi