Developing Solid Oral Dosage Forms: Pharmaceutical Theory and Practice

1176 Pages·2016·23.18 MB·English

by  Yihong Qiu, Yisheng Chen, Geoff G.Z. Zhang, Lawrence Yu, Rao V. Mantri (eds.)

DEVELOPING SOLID ORAL DOSAGE FORMS
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DEVELOPING
SOLID ORAL
DOSAGE FORMS
Pharmaceutical Theory & Practice
SECOND EDITION
Edited by
Y Q
IHONG IU
OralDrugProducts,ManufacturingScienceandTechnology,AbbVie,Inc.,NorthChicago,IL,UnitedStates
Y C
ISHENG HEN
NovastLaboratories,Ltd.,Nantong,China
G G. Z. Z
EOFF HANG
DrugProductDevelopment,ResearchandDevelopment,AbbVie,Inc.,NorthChicago,IL,UnitedStates
L Y
AWRENCE U
OfficeofPharmaceuticalQuality,CenterforDrugEvaluationandResearch,USFoodandDrugAdministration,
SilverSpring,MD,UnitedStates
R V. M
AO ANTRI
DrugProductScience&Technology,Bristol-MyersSquibb,NewBrunswick,NJ,UnitedStates
AMSTERDAM(cid:129)BOSTON(cid:129)HEIDELBERG(cid:129)LONDON
NEWYORK(cid:129)OXFORD(cid:129)PARIS(cid:129)SANDIEGO
SANFRANCISCO(cid:129)SINGAPORE(cid:129)SYDNEY(cid:129)TOKYO
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Dedication
This work isdedicated to Drs. R.D.Schoenwald, J.Keith Guillory,L.E.Matheson,the late D.J.W.Grant,
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Contents
List of Contributors xiii 4. API Solid-Form Screening and Selection
M.Y.GOKHALEANDR.V.MANTRI
4.1 Introduction 85
I
4.2 Solid-FormSelectionConsiderations 86
4.3 ScreeningSolid-FormsofAPI 102
THEORIES AND TECHNIQUES IN
4.4 IdentificationandAnalysisofForms 105
THE CHARACTERIZATION OF DRUG 4.5 Conclusions 107
SUBSTANCES AND EXCIPIENTS 4.6 CaseStudies 107
References 109
1. Solubility of Pharmaceutical Solids 5. Drug Stability and Degradation Studies
R.V.MANTRI,R.SANGHVI,ANDH.(J.)ZHU D.ZHOU,W.R.PORTERANDG.G.Z.ZHANG
1.1 Introduction 3 5.1 Introduction 113
1.2 ThermodynamicsofSolutions 5 5.2 ChemicalStability 113
1.3 TheoreticalEstimationofSolubility 6 5.3 CommonPathwaysofDrugDegradation 128
1.4 SolubilizationofDrugCandidates 10 5.4 ExperimentalApproachestoStudyingtheChemical
1.5 ExperimentalDeterminationofSolubility 18 DegradationofDrugs 134
References 21 5.5 PhysicalStabilityandPhaseTransformations 140
5.6 PhaseTransformationsDuringPharmaceutical
Processing 142
2. Crystalline and Amorphous Solids
References 146
G.G.Z.ZHANGANDD.ZHOU
2.1 Introduction 23 6. Excipient Compatibility and Functionality
2.2 DefinitionsandCategorizationofSolids 23
A.S.NARANG,R.V.MANTRIANDK.S.RAGHAVAN
2.3 ThermodynamicsandPhaseDiagrams 25
2.4 PharmaceuticalRelevanceandImplications 34 6.1 Introduction 151
2.5 TransformationsAmongSolids 38 6.2 ExcipientFunctionality 152
2.6 MethodsofGeneratingSolids 42 6.3 ExcipientCompatibility 155
2.7 AmorphousDrugsandSolidDispersions 43 6.4 ExcipientVariability 169
2.8 SpecialTopics 52 6.5 RiskAssessmentofDrug-ExcipientIncompatibilities
References 53 andMitigationStrategies 174
6.6 Conclusions 175
References 175
3. Solid-State Characterization and Techniques
D.LAWANDD.ZHOU
7. Polymer Properties and Characterization
3.1 Introduction 59 J.BRADY,T.DU¨RIG,P.I.LEEANDJ.-X.LI
3.2 Microscopy 60
3.3 PowderX-rayDiffraction 64 7.1 Introduction 181
3.4 ThermalAnalysis 67 7.2 BasicConceptsandCharacterizationofPolymeric
3.5 VibrationalSpectroscopy 72 Materials 185
3.6 MoistureSorption 79 7.3 CommonlyUsedPolymerExcipientsinSolidOral
3.7 HyphenatedTechniques 81 Products 206
3.8 Conclusion 82 7.4 Conclusion 220
References 82 References 221
vii
viii
CONTENTS
8. Interfacial Phenomena 12. Oral Drug Absorption: Evaluation and
Prediction
E.HADJITTOFIS,S.C.DAS,G.G.Z.ZHANGANDJ.Y.Y.HENG
Y.YANG,Y.ZHAO,A.YU,D.SUNANDL.X.YU
8.1 Interfaces 225
8.2 FundamentalIntermolecularForces 226 12.1 Introduction 331
8.3 ThermodynamicsofParticlesinElectrolyteSolutions 228 12.2 AnatomyandPhysiologyoftheGITract 331
8.4 SurfaceTensionandSurfaceEnergy 229 12.3 BiopharmaceuticsClassificationSystem 332
8.5 ThermodynamicsofWetting 232 12.4 IntestinalPermeabilityEvaluation:CulturedCells 338
8.6 Solid(cid:1)VaporInterface 236 12.5 IntestinalPermeabilityEvaluation:ExVivo 342
8.7 InterfacialPhenomenon(Solid(cid:1)Solid) 241 12.6 InSilicoMethods 346
8.8 FutureDirections—Opinions 246 12.7 InVivoMethodstoDetermineOralDrug
References 247 Absorption 347
12.8 FoodEffectsonDrugIntestinalAbsorption 348
12.9 RegionalDrugAbsorptionAlongGI 350
9. Fundamental of Diffusion and Dissolution
12.10 FutureTrends 352
Y.CHEN,J.WANGANDD.R.FLANAGAN 12.11 Conclusions 352
Disclaimer 352
9.1 FundamentalofDiffusion 253
References 352
9.2 FundamentalsofDissolution 262
References 270
13. Dissolution Testing of Solid Products
10. Particle, Powder, and Compact
Y.CHEN,Z.GAOANDJ.Z.DUAN
Characterization
13.1 Introduction 355
G.E.AMIDON,P.J.MEYERANDD.M.MUDIE
13.2 TheoryofDissolutionTestforSolidDrugProducts 356
10.1 Introduction 271 13.3 CurrentTechnologyandInstrumentationfor
10.2 ParticleSizeCharacterization 271 DissolutionTesting 358
10.3 PowderCharacterization 276 13.4 RegulatoryConsiderations 364
10.4 Compact(MechanicalProperty)Characterization 281 13.5 Summary 378
10.5 Conclusions 290 References 379
References 290
14. Bioavailability and Bioequivalence
II
H.ZHU,B.V.LI,R.S.UPPOOR,M.MEHTAANDL.X.YU
BIOPHARMACEUTICAL
14.1 GeneralBackground 381
AND PHARMACOKINETIC 14.2 DefinitionsandKeyConcepts 382
14.3 GeneralComponentsofBAandBEStudies 384
EVALUATIONS OF DRUG
14.4 DataAnalysisforBAandBEStudies 387
MOLECULES AND DOSAGE FORMS 14.5 SpecialTopicsforBAandBEAssessment 389
14.6 BiowaiverandBCS 393
14.7 SummaryandFuturePerspectives 395
11. Oral Absorption Basics: Pathways and References 395
Physicochemical and Biological Factors Affecting
Absorption
15. Predictive Biopharmaceutics and
L.ZHU,L.LU,S.WANG,J.WU,J.SHI,T.YAN,C.XIE,Q.LI,
Pharmacokinetics: Modeling and Simulation
M.HUANDZ.LIU
Y.YANG,Y.ZHAO,J.Z.DUAN,P.ZHAO,L.ZHAOANDX.ZHANG
11.1 BarrierstoOralDrugDelivery 297
11.2 PathwaysofDrugAbsorption 298 15.1 Introduction 399
11.3 PathwaysofDrugMetabolism 307 15.2 ModelingandSimulationApproachesfor
11.4 PathwaysofDrugElimination 312 BiopharmaceuticsandPK 400
11.5 CouplingofEnzymesandEffluxTransporters 315 15.3 ApplicationofBiopharmaceuticsandPKModeling
11.6 RegulationofTransportersandEnzymesbyNuclear andSimulationinDrugDevelopment 407
Receptors 319 15.4 ApplicationofBiopharmaceuticsandPKModeling
11.7 PhysicochemicalFactorsAffectingDrugAbsorption 321 andSimulationinRegulatoryActivities 408
11.8 BiologicalFactorsAffectingDrugAbsorption 323 15.5 Summary 409
References 325 References 409
ix
CONTENTS
16. In Vitro/In Vivo Correlations: Fundamentals, 19. Rational Design of Oral Modified-Release
Development Considerations, and Applications Drug Delivery Systems
Y.QIUANDJ.Z.DUAN Y.QIUANDP.I.LEE
16.1 Introduction 415 19.1 Introduction 519
16.2 DevelopmentandAssessmentofanIVIVC 416 19.2 OralMRTechnologiesandDrugDeliverySystems 521
16.3 ConsiderationsinIVIVCDevelopment 430 19.3 RationalDesignofModifiedReleaseSystems 538
16.4 IVIVCDevelopmentApproach 435 19.4 Summary 550
16.5 ApplicationsandLimitations 439 References 550
16.6 CaseStudies 441
16.7 Summary 447
20. Product and Process Development of Solid
References 447
Oral Dosage Forms
Y.QIU,X.HE,L.ZHUANDB.CHEN
III
20.1 Introduction 555
DESIGN, DEVELOPMENTAND 20.2 DevelopmentofSolidDosageForms 556
20.3 TechnologyTransfer 574
SCALE-UP OF FORMULATION
20.4 CaseStudies 578
AND MANUFACTURING PROCESS
20.5 IntellectualPropertyConsiderations 587
20.6 Summary 588
References 589
17. Oral Formulations for Preclinical Studies:
Principle, Design, and Development Considerations
21. Analytical Development and Validation
Y.GAO,C.GESENBERGANDW.ZHENG for Solid Oral Dosage Forms
17.1 Introduction 455 X.(F.)FANG,G.CARRANDR.C.FREEZE
17.2 ConsiderationsinDesigningFormulationsfor
21.1 AnalyticalMethodDevelopmentandValidation
PreclinicalSpecies 456
Strategy 593
17.3 UseofAPIPropertiestoGuideFormulationDesign 460
21.2 CategoryofAnalyticalMethodandMethod
17.4 FormulationsforBCSClassI/IIICompounds 463
Development 595
17.5 FormulationsforBCSClassII/IVCompoundsUsing
21.3 AnalyticalMethodValidation 597
EnablingTechnologies 465
21.4 MethodTransfers 606
17.6 EvaluatingFormulationPerformancebyInVitro
21.5 CaseStudies 607
Dissolution 482
21.6 Conclusions 610
17.7 RationaleSelectionofFormulationsSuitablefor
References 610
IntendedStudies 486
17.8 CaseStudy 488
Acknowledgments 491 22. Statistical Design and Analysis of Long-Term
References 491 Stability Studies for Drug Products
D.LEBLOND
18. Rational Design for Amorphous Solid
22.1 StabilityStudyObjectives 613
Dispersions
22.2 RegulatoryGuidance 613
A.NEWMAN 22.3 TestMethodsandDataManagement 614
22.4 ModelingInstability 615
18.1 Introduction 497
22.5 Long-TermStabilityStudyDesign 618
18.2 KeyComponentsofAmorphousSolidDispersions 497
22.6 DeterminationofShelfLife 625
18.3 CharacterizationofAmorphousDispersions 499
22.7 ReleaseLimitEstimation 628
18.4 ScreeningandSelectionofAmorphousSolid
22.8 ProbabilityofFutureOOSStabilityTestResults 629
Dispersions 501
AppendixASampleData 634
18.5 StabilityConsiderations 504
References 634
18.6 SolubilityandDissolutionConsiderations 505
18.7 MethodsofManufacturingAmorphousSolid
Dispersions 507 23. Packaging Selection for Solid Oral Dosage Forms
18.8 DosageFormDevelopmentConsiderations 509
Y.CHEN
18.9 CaseStudies 509
18.10 Conclusions 515 23.1 Introduction 637
References 515 23.2 MaterialConsiderations 638