Biopharmaceutics : From Fundamentals to Industrial Practice /: From Fundamentals to Industrial Practice. (2021)

• Record Type: Book
• Further Information: Note: Hannah Batchelor.
• Editors: Batchelor, Hannah
• Contents: List of Contributors xv Foreword xvii 1 An Introduction to Biopharmaceutics 1; Hannah Batchelor 1.1 Introduction 1 1.2 History of Biopharmaceutics 1 1.3 Key Concepts and Definitions Used Within Biopharmaceutics 3 1.4 The Role of Biopharmaceutics in Drug Development 6 1.5 Conclusions 8 2 Basic Pharmacokinetics 9; Hamid A. Merchant 2.1 Introduction 9 2.2 What is ‘Pharmacokinetics’? 9 2.3 Pharmacokinetic Profile 10 2.4 Bioavailability 12 2.5 Drug Distribution 13 2.6 Volume of Distribution 15 2.7 Elimination 16 2.7.1 Metabolism 16 2.7.2 Excretion 17 2.8 Elimination Half-Life (t ½) 19 2.9 Elimination Rate Constant 20 2.9.1 Clearance 20 2.10 Area Under the Curve (AUC) 21 2.11 Bioequivalence 22 2.12 Steady State 23 2.13 Compartmental Concepts in Pharmacokinetics 24 2.14 Concept of Linearity in Pharmacokinetics 25 2.15 Conclusions 28 3 Introduction to Biopharmaceutics Measures 31; Hannah Batchelor and Pavel Gershkovich 3.1 Introduction 31 3.2 Solubility 31 3.3 Dissolution 33 3.4 Permeability 34 3.5 Absorptive Flux 35 3.6 Lipinsky’s Rule of 5 35 3.6.1 Molecular Weight 36 3.6.2 Lipophilicity 36 3.6.3 Hydrogen Bond Donors/Acceptors 37 4 Solubility 39; Hannah Batchelor 4.1 Definition of Solubility 39 4.2 The Importance of Solubility in Biopharmaceutics 39 4.3 What Level of Solubility Is Required? 40 4.4 Solubility-Limited Absorption 41 4.5 Methods to Assess Solubility 41 4.6 Brief Overview of Forces Involved in Solubility 42 4.6.1 van der Waals Interactions 42 4.6.2 Hydrogen Bonding 42 4.6.3 Ionic Interactions 43 4.7 Solid-State Properties and Solubility 43 4.8 pH and Drug Solubility 43 4.9 Solvents 44 4.9.1 Biorelevant Solubility 45 4.9.2 Buffer System – Phosphate vs Bicarbonate 45 4.9.3 Solubilisation by Surfactants 45 4.9.4 Solubilisation During Digestion 47 4.9.5 Excipients and Solubility 47 4.10 Risk of Precipitation 48 4.11 Solubility and Link to Lipophilicity 49 4.12 Conclusions 49 5 Permeability 51; Chris Roe and Vanessa Zann 5.1 Introduction 51 5.2 Enzymes, Gut Wall Metabolism, Tissue Permeability and Transporters 51 5.2.1 Enzymes 52 5.2.2 Drug Transporters 54 5.2.3 Efflux Transporters 55 5.2.4 Transporters of Greatest Relevance to Oral Biopharmaceutics 56 5.2.5 Regulatory Overview of Transporter Effects on Biopharmaceutics 58 5.2.6 Regional Expression and Polymorphism of Intestinal Transporters and Impact of Drug Variability 58 5.3 Applications and Limitations of Characterisation and Predictive Tools for Permeability Assessment 59 5.3.1 In Silico Tools: Predictive Models for Permeability 59 5.3.2 in vitro Tools 60 5.3.2.1 PAMPA 60 5.3.2.2 Cell Lines 61 5.3.3 ex vivo Tools 63 5.3.3.1 Ussing Chambers 63 5.3.3.2 Everted Intestinal Sac/Ring 65 5.3.4 In Situ Tools 66 5.3.4.1 Closed-Loop Intestinal Perfusion 66 5.3.4.2 Single-Pass Intestinal Perfusion 66 5.3.4.3 Intestinal Perfusion with Venous Sampling 67 5.3.4.4 Vascularly Perfused Intestinal Models 67 5.4 in vivo Tools 67 5.5 Conclusion 69 6 Dissolution 75; Hannah Batchelor and James Butler 6.1 Introduction 75 6.2 Purpose of Dissolution Testing 75 6.2.1 Dissolution Versus Solubility 76 6.3 History of Dissolution Testing 77 6.4 Compendial (Pharmacopeial) Dissolution Apparatus 78 6.4.1 USP1 and 2 Apparatus 78 6.4.2 USP3 Apparatus 79 6.4.3 USP4 Apparatus 80 6.4.4 USP5 Apparatus 82 6.4.5 USP6 Apparatus 82 6.4.6 USP7 Apparatus 82 6.4.7 Intrinsic Dissolution Rate (IDR) Apparatus 83 6.4.8 Micro-dissolution Apparatus 83 6.5 Dissolution Media Selection 83 6.5.1 Biphasic Dissolution Media 84 6.6 Dissolution Agitation Rates 84 6.7 Reporting Dissolution Data 85 6.8 In Vitro In Vivo Relationships and Correlations (IVIVR/IVIVC) 86 6.8.1 Convolution and Deconvolution of Dissolution Data 87 6.9 Evolution of Biorelevant Dissolution Testing 88 6.9.1 Biorelevant Dissolution Media 88 6.9.2 Dissolution Testing to Mimic GI Transit 93 6.9.3 Dissolution Testing to Mimic Motility/Hydrodynamic Conditions 94 6.9.4 Dissolution Testing to Incorporate Permeability 95 6.10 Conclusions 96 7 Biopharmaceutics to Inform Candidate Drug Selection and Optimisation 103; Linette Ruston 7.1 Introduction 103 7.2 Oral Product Design Considerations During Early Development 103 7.3 Biopharmaceutics in Drug Discovery 105 7.3.1 Pre‐Clinical Studies 106 7.4 Biopharmaceutics Assessment 107 7.4.1 Solubility 107 7.4.2 Permeability 107 7.4.3 Dissolution 108 7.4.4 Biopharmaceutics Classification System 108 7.4.5 Lipophilicity 109 7.4.6 pK a 109 7.4.7 Molecular Size 109 7.4.8 Crystallinity 109 7.4.9 In Vivo Pre‐Clinical Studies 109 7.4.10 In Silico Modelling 110 7.4.11 Human Absorption/Dose Prediction 110 7.5 Output of Biopharmaceutics Assessment 110 7.5.1 New Modalities/Complex Delivery Systems Within Early Development 112 7.6 Influence/Optimise/Design Properties to Inform Formulation Development 112 7.6.1 Fraction Absorbed Classification System 113 7.7 Conclusion 114 8 Biopharmaceutics Tools for Rational Formulation Design 117; Panagiota Zarmpi, Mark McAllister, James Butler, and Nikoletta Fotaki 8.1 Introduction 117 8.2 Formulation Development to Optimise Drug Bioavailability 118 8.3 Traditional Formulation Strategies 119 8.3.1 Decision Making for Conventional or Enabling Formulations 119 8.4 Decision Trees to Guide Formulation Development 119 8.4.1 Decision Trees Based on Biopharmaceutics Classification System (BCS) 119 8.4.2 Decision Trees Based on Developability Classification System (DCS) 121 8.4.3 Expanded Decision Trees 122 8.5 Computational Tools to Guide Formulation Strategies 124 8.5.1 Statistical Tools 124 8.5.2 Physiologically Based Pharmacokinetic/Biopharmaceutics Models 125 8.6 Decision- Making for Optimising Enabling Formulations 125 8.7 Decision Trees for Enabled Formulations 127 8.7.1 Statistical Tools 128 8.7.2 Physiologically Based Pharmacokinetic/Biopharmaceutics Models 128 8.8 System-Based Formulation Strategies 128 8.8.1 Quality by Design 128 8.8.2 Tools to Identify Quality Target Product Profile 129 8.9 Biopharmaceutics Risk Assessment Roadmap (BioRAM) 131 8.9.1 Tools to Identify Quality Target Product Profile 131 8.10 Conclusions 132 9 Biopharmaceutic Classification System 139; Hannah Batchelor and Talia Flanagan 9.1 Description and History of the BCS 139 9.2 BCS-Based Criteria for Solubility, Dissolution and Permeability 139 9.3 BCS-Based Biowaivers 141 9.4 Regulatory Development of BCS-Based Biowaivers 142
• Edition: 1st
• Publisher Details: Wiley
• Publication Date: 2021
• Extent: 1 online resource (320 pages)
• Languages: English
• ISBNs: 9781119678373
• Access Rights: Legal Deposit; Only available on premises controlled by the deposit library and to one user at any one time; The Legal Deposit Libraries (Non-Print Works) Regulations (UK).
• Access Usage: Restricted: Printing from this resource is governed by The Legal Deposit Libraries (Non-Print Works) Regulations (UK) and UK copyright law currently in force.