Pharmaceutical Dissolution Testing, Bioavailability, and Bioequivalence: Science, Applications, and Beyond

Cover
Title Page
Copyright
Contents
Foreword
Foreword
Preface
Acknowledgments
Chapter 1 Pharmaceutical Dissolution Testing: Fundamentals and Essential Applications (An Overview)
1.1 Introduction and Objective(s)
1.2 Science of Dissolution Over Past 120+ Years
1.2.1 Journey from Quality Control (QC) to Development
1.3 Fundamentals of Dissolution Testing (An Overview)
1.4 Factors Influencing Dissolution Test(ing)
1.5 Pharmaceutical Product Life Cycle: Role of Dissolution (An Overview)
1.6 Dissolution Test(ing): What It Is and What It Is Not!
1.7 Need for This Textbook
1.8 Summary and Concluding Remarks
References
Chapter 2 Bioavailability (BA) and Bioequivalence (BE): Fundamentals and Applications in Drug Product Development
2.1 Introduction and Objective(s)
2.2 Definitions
2.3 Bioequivalence (BE) Testing: Basics, Advances, and Global Perspectives
2.3.1 BA/BE Study Designs
2.3.2 Sample Size, n
2.3.3 BE (Acceptance) Criteria and Statistical Considerations
2.3.4 Bioequivalence (BE) Studies: Role of Modeling and Simulations
2.3.5 Surrogates to BE
2.3.6 PD Endpoint‐Based and Clinical Endpoint‐Based BE Assessment
2.3.7 Regulatory Requirements
2.4 Current Challenges and Solutions (Insight into Chapter 14)
2.5 Summary and Concluding Remarks
References
Chapter 3 Solubility, Dissolution, Permeability, and Classification Systems
3.1 Introduction and Objective(s)
3.2 Definitions
3.3 Solubility Versus Solubilization: What Is Critical in Development?
3.3.1 Theories of Solubilization
3.3.2 Solubility: Challenges in Drug Development!
3.3.3 Solubility Enhancement: Purpose, Theoretical and Practical Considerations!
3.4 Dissolution: Intrinsic Versus Apparent!
3.4.1 Theories of Dissolution
3.4.1.1 Noyes–Whitney Theory (1897)
3.4.1.2 Brunner and Tolloczko Theory (1900)
3.4.1.3 Nernst and Brunner Theory (1904)
3.4.2 Intrinsic Versus Apparent Dissolution
3.5 Permeability Versus Permeation (Process): What Is Critical for Bioefficacy!
3.6 Classification Systems: Theoretical Versus Pragmatic Considerations!
3.7 Summary and Concluding Remarks
References
Chapter 4 Understanding the Mechanics of Dissolution: Mathematical Models and Simulations
4.1 Introduction and Objective(s)
4.2 Mechanics of Dissolution: Theories, Presumptions, and Reality Check
4.3 Dissolution Theories/Models
4.4 Dissolution Mechanics (Model‐Dependent Methods)
4.4.1 Zero Order
4.4.2 First‐Order Model (Gibaldi–Feldman Model 1967)
4.4.3 Makoid–Banakar Model (1993)
4.4.4 Hixson and Crowell Model (1931)
4.4.5 Higuchi Model (1961, 1963, 1967)
4.4.6 Baker–Lonsdale (1974)
4.4.7 Korsmeyer–Peppas Model (1983)
4.4.8 Hopfenberg Model (1976)
4.4.9 Gompertz Distribution Model
4.4.10 El‐Yazigi Model (1981)
4.5 Dissolution Mechanics (Model‐Independent Methods)
4.5.1 Weibull Distribution Model (1951)
4.5.2 Statistical Mean Time Concept/Model (1982)
4.5.3 (Other) Statistical Regression‐Based Models
4.5.4 Sequential Model
4.5.5 Density Function Theory (DFT)
4.6 Relevance of Mathematical Modeling of Dissolution
4.7 Purposeful Modeling and Simulation
4.8 Summary and Concluding Remarks
References
Chapter 5 Dissolution Testing Methods: Necessity Is the Mother of Invention!
5.1 Introduction and Objective(s)
5.2 Need for Dissolution Testing Method
5.3 Dissolution Testing Methods
5.3.1 Science of Dissolution
5.3.2 Intrinsic and Apparent Dissolution Methods
5.3.3 Compendial Methods Versus Regulatory Perspective
5.3.4 Predictive Testing Methods and “Biorelevant Dissolution” Methods
5.4 Necessity Is the Mother of Invention!
5.4.1 Controlled Release Parenteral Systems Including Drug‐Eluting Stents
5.4.2 Pharmaceutical Formulations for the Oral Cavity
5.4.2.1 Soft Gelatin Capsules (SGC): Oral Delivery and Rectal Inserts
5.4.3 Inhalation Products
5.4.4 Semisolid Pharmaceutical Systems Including Transdermal Drug Delivery Systems (TDDSs)
5.4.5 Nanotechnology‐Based Systems: Nanobiomedicine Formulations
5.4.6 Others
5.5 The Perpetual Struggle
5.6 Concluding Remarks
References
Chapter 6 Essentials of Dissolution Testing of Pharmaceutical Systems
6.1 Introduction and Objective(s)
6.2 Objectives of Dissolution Testing of Pharmaceutical Systems
6.3 Oral Solid Dosage Forms (SDFs)
6.3.1 Immediate Release/Rapid Release SDFs
6.3.1.1 Conventional IR SDFs (Focus: Recent Advances in Solubility Enhancement!)
6.3.1.2 Chewable: Tablets and Gums
6.3.2 Modified Release (MR) SDFs
6.3.3 Advanced/Innovative MR‐SDFs
6.4 Oral Liquid Dosage Forms
6.4.1 Rapid Release Systems (RRSs)
6.5 Non‐oral Dosage Forms
6.5.1 Topical Dosage Forms
6.5.1.1 Traditional Topical Dosage Forms
6.5.1.2 Transdermal Drug Delivery Systems
6.5.1.3 Nasal, Ocular, Otic, Vaginal, and Rectal Dosage Forms
6.5.2 Parenteral Dosage Forms
6.6 Nanotechnology‐Based Pharmaceutical Systems
6.7 Nutraceuticals and Natural Products
6.8 Concluding Remarks: Need for Purposeful Dissolution/Release Testing!
References
Chapter 7 Dissolution/Release Test Data (Profile): Requirements, Analyses, and Regulatory Expectations
7.1 Introduction and Objective(s)
7.2 Academic Curiosity
7.3 Early Development
7.4 Product Development Stage
7.5 Comparative Analyses
7.6 Summary and Concluding Remarks
References
Chapter 8 Automation in Dissolution Testing: Recent Advances and Continuing Challenges!
8.1 Introduction and Objective(s)
8.2 Automated Dissolution Testing: Why and What to Automate?
8.3 Challenges in Automation of Dissolution Test(ing)
8.4 Automation in Dissolution Testing: Looking Forward!
8.5 Concluding Remarks
References
Chapter 9 In vitro–In vivo Correlations (IVIVCs): What Makes Them Challenging!
9.1 Introduction and Objective(s)
9.2 Basic Model, Scheme, and Assumptions
9.3 Mechanics for Determination of IVIVC
9.4 BCS and IVIVC
9.5 IVIVC in New Drug Development vis‐à‐vis Generic Drug Development
9.6 IVIVCs in Topical/Transdermal Drug Delivery Systems (TDDSs)
9.7 Nonlinear IVIVCs
9.8 Validation of IVIVC Prediction Error (PE)
9.9 IVIVC in Drug Product Life Cycle: What Is the Ultimate Objective?
9.10 Summary and Conclusions
References
Chapter 10 Biorelevant Dissolution/Release Test Method Development for Pharmaceutical Dosage Forms
10.1 Introduction and Objective(s)
10.2 General Considerations in BDM Development
10.3 Oral Drug Delivery Systems
10.3.1 Challenges in the Simulation of GI Biorelevant Factors: Motility and Hydrodynamics
10.3.2 Biorelevant Dissolution Media for Oral Drug Delivery Systems
10.4 Inhalation Drug Delivery Systems
10.5 Parenteral Drug Delivery Systems
10.6 Other Drug Delivery Systems
10.7 The Roadmap
10.8 Summary and Concluding Remarks
References
Chapter 11 Bioavailability Prediction Software: Hype or Reality!
11.1 Introduction and Objective(s)
11.2 The Need for Simulations and Predictions in Drug Product Development
11.3 Simulation and Prediction of In Vivo Performance: The Catch‐22 Situation!
11.4 Bioavailability (BA)/Bioequivalence (BE) Simulation Software: What They Do and Do Not!
11.5 Appreciating and Depreciating Potential Utility of BA Prediction Software
11.6 Concluding Remarks
References
Chapter 12 Challenges and Unique Applications of IVIVC in Drug Development
12.1 Introduction and Objective(s)
12.2 USP <1088> and US FDA Guidance for Industry (1997): Operational Challenges
12.3 Applications of IVIVC(s)
12.4 Prospective IVIVC(s)
12.4.1 Background
12.4.2 Process
12.4.3 Application
12.4.3.1 Unique Application of IVIVC
12.5 Retrospective IVIVC(s): Responding to Agency Queries!
12.6 Summary and Concluding Remarks
References
Chapter 13 Dissolution Testing in Generic Drug Development: Methods, Requirements, and Regulatory Expectations/Requirements
13.1 Introduction and Objective(s)
13.2 Generic Drug Development Process: Role of Dissolution Testing
13.2.1 Preformulation
13.2.2 Prototype Formulation
13.2.3 Prospective Development: IVIVC with BE as the Objective!
13.2.4 Pilot BE to Pivotal BE
13.3 Generic Pharmaceutical Systems: Role of Dissolution
13.3.1 Traditional: Para III Formulations – Rush to “First to File”
13.3.2 Para IV Formulations
13.3.3 Exploring 505(b)(2) Opportunities
13.3.4 Differentiated Products and/or Incremental Innovations
13.3.5 Supergenerics: Are They?
13.3.6 Complex Generics
13.4 Generics: Finished Products – Role of Dissolution Testing
13.4.1 Tentative Approval to Final Approval: Setting QC Specifications!
13.4.2 Biowaivers: Global Considerations and Perspectives!
13.4.3 Regulatory Queries and Responses
13.5 Summary and Concluding Remarks
References
Chapter 14 Successful Bioequivalence Investigations: Current Challenges and Possible Solutions!
14.1 Introduction and Objective(s)
14.2 Understanding Challenges and Approaches to Overcome Them!
14.2.1 Oral Dosage Forms
14.2.1.1 Highly Variable Drugs (HVDs)
14.2.1.2 Oral Dosage Forms: Locally Acting
14.2.2 Narrow Therapeutic Index (NTI) Drugs
14.2.3 Topical Dosage Forms
14.2.3.1 Ophthalmic Dosage Forms
14.2.4 Oral Inhalation Products
14.2.5 Complex Generics
14.2.6 Nutraceuticals and Natural Products
14.3 Concluding Remarks
References
Chapter 15 Beyond Guidance(s): Convincing Regulatory Authorities Through Creative Dissolution Data Interpretation
15.1 Introduction and Objective(s)
15.2 Regulatory Guidance(s): Reading Versus Understanding!
15.3 Regulatory Submission: Premise and Expectation(s)
15.4 Handling Regulatory Query/Deficiency: Efficient and Satisfying Response
15.5 Winning an Argument: Three Cs to Succeed!
15.6 Sample Case Study(ies)
15.7 Summary and Concluding Remarks
References
Chapter 16 Biosimilars: The Emerging Frontier for Generics – Role of Dissolution Testing!
16.1 Introduction and Objective(s)
16.2 Generics, (Bio)betters, and Biosimilars: What Are They?
16.3 Regulatory Approval Process (Brief): Focus on Efficacy!
16.4 Role of Solubility and Dissolution
16.5 Concluding Remarks
References
Chapter 17 Patentability of Drug Product Based on Dissolution Data: Intellectual Property Considerations!
17.1 Introduction and Objective(s)
17.2 Patentability and the Patent Process (Brief): Scientist's Perspective
17.2.1 Is Solubility and Dissolution Patentable: Scientist's Perspective
17.3 Pharmaceutical Product: Patentability and Role of Dissolution Testing
17.4 Patentability: Double‐Edged Sword!
17.5 Concluding Remarks
References
Chapter 18 Setting Up Clinical Therapeutics Safety‐Based QC Specifications for Dissolution Testing of a Finished Product
18.1 Introduction and Objective(s)
18.2 Critical Quality Attributes (CQA): \textit {Role of In vitro Dissolution as a QC Test}!
18.3 Clinical Drug Product Performance: \textit {Adequate or Predictable}!
18.4 Clinically Relevant Specifications (CRS): \textit {Basics and Challenges}!
18.4.1 Setting Up CRDS or CRS
18.5 Idealism and Pragmatism Versus Realism!
18.6 Concluding Remarks
References
Chapter 19 Unlocking the Mystery(ies) While Predicting Bioavailability from Dissolution
19.1 Introduction and Objective(s)
19.2 The IVIVC Model and Objective(s) of IVIVC
19.3 Challenges Encountered in Predicting Bioavailability from Dissolution
19.4 What Are We Doing Now?
19.4.1 Mathematical Modeling: Limitations and Feel Good Phenomena!
19.4.2 BCS and Its Relation to Drug Formulation's Dissolution Performance
19.4.3 The Application (or the Lack) of f1 and f2 Parameters
19.4.4 Dissolution Data Banks, Agency Recommendations, and Compendial Monographs
19.4.5 Dissolution Testing Apparatuses (Choice Versus Selection!)
19.4.6 Advent of Biophysiologically Relevant Dissolution Media(um)
19.4.7 What Are We Missing in This Picture?
19.5 What We Should Be Doing! The Way Forward: The Missing Link!
19.6 Advent of IVRT, IVPT, PBPK, and PBAM
19.6.1 Role of IVRT, IVPT, and PBAM in Predicting In Vivo Absorption of Drug from Oral Solid Dosage Forms
19.7 Summary and Concluding Remarks
References
Index
EULA