Post on 19-Aug-2018
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PHARMACEUTICAL SPRAY DRYINGA Method of Choice to address Low API Solubility,Poor Bioavailability and Drug Formulation Challenges
POORLY SOLUBLE APIs INCREASINGLY FOUND AMONG NEW DRUG DEVELOPMENTS
0%
50%
100%
Marketed Drugs Pipeline Drugs
BCS II BCS IV BCS I BCS III
POORLY SOLUBLEAPIs, 40%
POORLY SOLUBLEAPIs,90%
• Low aqueous API solubility and related poor bioavailability pose a significant hurdle for an efficient drug formulation, in particular for oral delivery
• The number of APIs insoluble in water has reached very high levels among NCEs due to in-creasing drug lipophilicity for better targeting enzymes and membrane proteins or because of increasing molecular complexity
• APIs within BCS Classes II and IV (Biopharmaceutical Classification System) having poor solubility and permeability are especially problematic and frequently found among pipeline developments
POOR API SOLUBILITY PRESENTS A GROWING CHALLENGE FOR DRUG PRODUCT FORMULATION AND DRUG DELIVERY
PARTICULAR BENEFITS OF SPRAY DRYING
• Highapplicabilitycombinedwithadvantageofreducedformulationcomplexity• IncreasinglyutilizedtoimprovesolubilitypropertiesandbioavailabilityofAPIsvia anamorphoussolidAPIdispersioninasuitablematrix• Convenientone-stepprocessconvertinganAPIfromaliquidform(e.g.solution, suspension)directlyintoapowderundermildconditionsandveryshort residencetimesuitableforthermallyunstableandsheersensitivecompounds• Established,robusttechnologyoperatedatindustrialcommercialscale fordecades• Highlyversatile,reproducibleprocessthatcanbescaleduptonearlyany productionsize(batchorcontinuousmode)withlowercost(equipment, utilities,cycletime)andbetterflexibilitythanlyophilization• ModifiesvariousparticlepropertiesofAPIpowderswithgooduniformity,such assizedistribution,dispersibility,flowability;increasedsurfacearea achievablewithoutasubsequentmillingstep• Veryusefulforinhalationproductsforparticlesizecontrol• Applicableforalargevarietyofbiopharmaceuticalsfromsmallmolecules toproteins• Convenienttoconvertoilycompoundsintopowdersviaadditionofsuitable adjuvantsduringtheprocess• Utilizedforimprovingdirectcompressibility,modifiedreleaseandtastemasking formulations,particlecoatingandmicroencapsulation• ImprovementofdosevariabilityandloweringrequireddoseleadingtolessAPI consumptionandcostsavingsduringclinicalstudies
SPRAYDRYINGISAPOWERFULTECHNOLOGYTOADDRESSAPISOLUBILITYCHALLENGES
• ExtensiveexperienceinpharmaceuticalspraydryingatHaverhill/UKsite• SiteoperatesundercGMPstandardsincontrolledenvironmentandhasregularly beeninspectedbyregulatoryauthoritiesincludingFDA,EMEAandMHRA• Capacitytosupportproductrequirementsfromclinicaltrialstolargecommercial scale• Feedstock(e.g.solution,suspension)canbepreparedonsiteorreceivedinliquid form;USPgradepurifiedwateravailable• Crystallinesolutionscanbere-dissolvedandspraydried• Stirredfeedsystems• Clean-In-Place(CIP)systemavailable• Environmentalcontrols• Supplementaldryingcapabilitiesavailable,e.g.fluidbed
SANOFICEPiAOFFERSPHARMACEUTICALSPRAYDRYINGFROMCLINICALTOCOMMERCIALSCALE
LABORATORYSPRAYDRYER
o 1.5liters/hourwaterevaporationrateat250oCinlettemperatureo Samplefeedupto65ml/houro Inlettemperature40-250oCo Dryingairthroughput38-73m3/houro Automaticjetde-blocking
INTERMEDIATESCALESPRAYDRYER
o Spraydriedproductvolumes>100mt/year(productdependent)o Highpressureortwofluidatomizationo 100liters/hourliquidflowrateo Temperaturerange:200oCinlet,140oCoutleto Bagfiltero Nitrogeninertionforflammablepowders
LARGESCALESPRAYDRYER
o Spraydriedproductvolumesbetween200and>1,000mt/year (productdependent)o Highpressureatomizationo 1,500liters/hourliquidflowrateo Onlinecontrolsystemsformeasuringgasandfeedflowrateo Internalcamerastomonitorspraypatternsandproductrecoveryperformanceo Temperaturerange:250oCinlet,140oCoutleto Bagfiltero Pneumatichammersandairsweepsystemforenhancedproductrecoveryo Explosionsuppressionsystemwithfiredetectionanddelugesystemtohandle flammablepowders
ANALYTICAL CAPABILITIES
Portfolio of online and offline analytical testing:
• ProcessAnalyticalTechnology(PAT) oNIR,Raman,Mid-IR,UV• ParticleSizeDistribution(Mastersizer)• ParticleMorphology• FeedDensity&FeedConcentration• DynamicVaporSorption(DVS)• MoistureAnalysis• X-RayFluorescence(XRF)• GC,GC-MS,HS-GC,Pyrolysis-GC-MS• HPLC• MS,LC-MS• DifferentialScanningCalometry(DSC)• ThermogravimetricAnalysis(TGA),TGA-MS• SizeExclusionChromatography• IonChromatography• Rheometry• NMR• InductivelyCoupledPlasma-OpticalEmissionSpectrometry(ICP-OES)• GelElectrophoresis• Titrimetry• Conductivity• Bulk/TapDensity
SANOFICEPiAOFFERSPHARMACEUTICALSPRAYDRYINGFROMCLINICALTOCOMMERCIALSCALE
April 2016 - photo credits: SANOFI
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