处方前研究.ppt

Preformulationstudy Preformulationstudy PhysicalandChemicalProperties BiopharmaceuticalProperties PharmacologicalandToxicologicalproperties PhysicalandChemicalProperties DescriptionoftheproductsDescriptionofthebusiness hygrooscopicity SolubilityandPka Textinhere Textinhere Textinhere Textinhere Title stability micromeritics hygroscopicity Compatibilityofexcipient MPandpolymorphism Textinhere Partitioncoefficient solubility Pka Dissociationconstants drugmustpossessaqueoussolubilityforthreaepeuticefficacy Ifthesolubilityofdrugislessthandesirable considerationmustbegiventoimproveitssolubility TheextentofdissociationinmanycasesishighlydependentonthePhofthemediumcontainingthedrugInformulationoftenthevehicleisadjustedtocertainPhtoabtainacertainlevelofionizationOrdissociationforsolubilityorstability Partitioncoefficient theoil waterpartitioncoefficient P isameasureofamolecule lipophiliccharacter DrugswhichhavebiggerPcanbeeasilyabsorbedwhentheyhavethesimiliarPkavalue P Conc Ofdruginoctanol Conc Druginwater whileoctanolisthemostcommonusedssolventduringthemeasurementoftheP andwhendrugexistasamonomerP Conc Ofdruginoctanol n Conc Druginwater whilethedrugexistsaspolymer Textinhere RelationbetweenPofbarbituratesandabsorptioninstomachofrats Polymorphicformsusuallyexhibitdifferentphysicochemicalproperties includingmeltingpointandsolubility Evaluationofcrystalstructure polymorphism andsolvateformisaveryimportantperformulationactivity Thechangeincrystalcharasteristicscaninfluencebioavailabilityandchemicalandphysicalstabilityandcanhaveimportantimplicationsindosageformprocessfunctions Oftenusedtodeterminethepurityofadrugandinsomecasesthecompatibilityofvarioussubtancesbeforeinclusioninthesamedosageform Requieddosageform polymorphism examples polymorphism AmongdifferentcrystaltypesofCimetidine typeAisthebestonebecauseofsolubility thedissolutionrateofthreetypesIndometacin isincreacedrespectlyinphosphatebuffer Byadjustingtheratioofvariouscrystalsofinsulin wecangetsuspensionwithdifferenteffectiveduration Duringtheproductionprocess manyfactorscanacceleratethechangesofcrystalforms suchasenvironmentalfactors humidity water solventandtechnologicalfactors spraydrying heatsterilization freeze dryingetc Atthesametime thechangeinstorageperiodalsoshouldbeconsideredVarioustechniquesareusedtodeterminethecrystalproperties polymorphismrm polymorphism Methodsusedtodeterminecrystalproperties Ramanspectroscopy hotstagemicroscopy X raydiffraction IR SS NMR Thermalanalysis methods hygroscopicity Whensoliddrugabsorbsmoisture itwillformaliquidmembraneonthesurfaceanddecompositionreactionhappens suchasacetylsalicylicacid penicillinGetc DetermineCRHofdrugpreformulationly choosingappropriateproducingandstoringenvironment Drugwhocanabsorbswaterfromsurroundingshasthepropertyofhygroscopicity ThedegreemainlydependsonRHofenvironment micromeritics stability Mainlycontainsshapesizeparticlesizedistributionpowderdensityadhesionmobilitywettability Usefulinprescriptioncomposition preparation choosingapproprateexcipientsetc Compatibilityofexcipient Compatibilityofsoliddosageforms Compatibilityofaqueoussolution Testmethod putthemixtureofdrugandexcipientsintoasealedbottleObserveifthereiaanyphysicalchangehappens thentestwithTLCorHPLCtoanalysiscontentchanges Testmethod mixdrugwithexcipientsolutionwiththepresenceofmetalionorantioxidant theresultcantellthestabilityofdrugandexcipientintheconditionofOxidation Illumination Thisisveryimportantindosagedesignofinjection BiopharmaceuticalProperties HighFirst passeffect prodrugb BemetabilizedwithhelpofenzymeSaturationc Inhibitenzymeofliver helpdecreasingmetabolismofotherdrugs a Bioavailabilityspeed b DegreeofBioavailability ADME Bioavailability pharmacologicalandtoxicologicalproperties pharmacodynamics