Biopharmaceutics

Explore the latest research in biopharmaceutics from leading contributors in the field

In Biopharmaceutics - From Fundamentals to Industrial Practice, distinguished Scientists from the UK's Academy of Pharmaceutical Sciences Biopharmaceutica Focus Group deliver a comprehensive examination of the tools used within the field of biopharmaceutics and their applications to drug development. This edited volume is an indispensable tool for anyone seeking to better understand the field of biopharmaceutics as it rapidly develops and evolves.

Beginning with an expansive introduction to the basics of biopharmaceutics and the context that underpins the field, the included resources go on to discuss how biopharmaceutics are integrated into product development within the pharmaceutical industry. Explorations of how the regulatory aspects of biopharmaceutics function, as well as the impact of physiology and anatomy on the rate and extent of drug absorption, follow.

Readers will find insightful discussions of physiologically based modeling as a valuable asset in the biopharmaceutics toolkit and how to apply the principles of the field to special populations. The book goes on to discuss:

• Thorough introductions to biopharmaceutics, basic pharmacokinetics, and biopharmaceutics measures

• Comprehensive explorations of solubility, permeability, and dissolution

• Practical discussions of the use of biopharmaceutics to inform candidate drug selection and optimization, as well as biopharmaceutics tools for rational formulation design

• In-depth examinations of biopharmaceutics classification systems and regulatory biopharmaceutics, as well as regulatory biopharmaceutics and the impact of anatomy and physiology

Perfect for professionals working in the pharmaceutical and biopharmaceutical industries, Biopharmaceutics - From Fundamentals to Industrial Practice is an incisive and up-to-date resource on the practical, pharmaceutical applications of the field.

Auteur

Edited by

Hannah Batchelor, Strathclyde Institute of Pharmacy and Biomedical Sciences.

Contenu

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 (t½) 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...