PHARMACEUTICAL SPRAY DRYING A Method of Choice to address Low API Solubility, Poor Bioavailability and Drug Formulation Challenges
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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