Fundamentals of Drug Delivery. (2021)

• Record Type: Book
• Further Information: Note: Heather A. E. Benson, Michael S. Roberts, Adrian C. Williams, Xiaowen Liang.
• Editors: Benson, Heather A. E; Roberts, Michael S; Williams, Adrian C; Liang, Xiaowen
• Contents: Preface xvii Part I Product Design, the Essence of Effective Therapeutics 1 1 Challenges and Innovations of Controlled Drug Delivery 3; Heather A.E. Benson and Michael S. Roberts 1.1 Background 3 1.2 Parenteral Dosage Forms 3 1.2.1 Intravenous Route (IV) 4 1.2.2 Intramuscular Route (IM) 5 1.2.3 Subcutaneous Route (SC) 5 1.2.4 Other Parenteral Routes 5 1.3 Oral Route and Delivery Systems 6 1.4 Nasal Drug Delivery 6 1.5 Pulmonary Drug Delivery 7 1.6 Transdermal Drug Delivery 7 1.7 Ocular Drug Delivery 9 1.8 Drug Delivery System Development Process 11 1.9 Conclusion 12 References 12 2 Challenges in Design of Drug Delivery Systems 15; Narasimha Murthy 2.1 Drug Properties to be Considered in Design of Controlled Release Products 19 2.2 Physicochemical Factors that Need to be Considered in Design of CRDDS 19 2.2.1 Dose Size 19 2.2.2 MolecularWeight/Size 19 2.2.3 Aqueous Solubility 21 2.2.4 Lipid Solubility and Partition Coefficient 25 2.2.5 Physicochemical Stability 26 2.3 Biopharmaceutical Properties that Deserve Consideration in Design of Controlled Release Products 26 2.3.1 Biological Half-life 26 2.3.2 Absorption 27 2.3.3 Metabolism 30 2.3.4 Presystemic Clearance 32 2.3.5 Margin of Safety 32 2.3.6 Adverse Effects 33 2.3.7 Therapeutic Need 33 2.3.8 Role of Circadian Rhythm 34 2.4 Conclusion 35 References 35 3 Drug Delivery of the Future (?) 39; Adrian Williams 3.1 Introduction 39 3.2 Therapeutic Indicators 40 3.3 Drugs of the Future 43 3.4 Delivering the Drugs of the Future 45 3.5 A View to the Longer Term? 47 3.6 Conclusion 50 References 50 4 The Pharmaceutical Drug Development Process: Selecting a Suitable Drug Candidate 53; Lionel Trottet 4.1 The Oral Drug Candidate: How to Get There and Questions to Answer 53 4.2 Challenges for Selecting a Topical Drug Candidate 55 4.3 Percutaneous Flux as a Surrogate Measurement of Skin Tissue Concentration 57 4.4 Learnings from Past Topical Drug Development of Factors Affecting Efficacy 58 4.5 Dermal Pharmacokinetics/Pharmacodynamics 62 4.6 Assessment of Systemic Exposure 63 4.7 Screening Cascade Approach to Select a Dermal Drug Candidate 64 4.7.1 Efficacy (Lack of Target Engagement) 64 4.7.2 Developability 65 4.7.3 Local Safety 65 4.7.4 Systemic Safety 65 4.8 Opportunities for Repurposing Molecules into Dermally Active Treatments for Cosmeceutical or Pharmaceutical Approaches 66 4.9 Conclusion 66 References 67 5 Preformulation and Physicochemical Characterization Underpinning the Development of Controlled Drug Delivery Systems 73; Ronak Savla and Julien Meissonnier 5.1 When Is a Controlled Drug Delivery System Needed? 73 5.2 Optimizing Drug Characteristics 74 5.3 Defining the Product Profile 75 5.4 Preformulation and Physicochemical Characterization Underpinning Development of CDD 77 5.4.1 Feasibility and Risk Assessment 78 5.4.2 Solubility and Dissolution Rate 79 5.4.3 Permeability 82 5.4.4 Drug and Drug Product Particle Sizes 83 5.4.5 Solid-State Chemistry 84 5.4.5.1 Crystallinity and Polymorphism 84 5.4.5.2 Salts 85 5.4.6 Stability 85 5.4.7 Excipient Compatibility 86 5.4.8 Bulk Powder Properties 87 5.4.9 Drug Metabolism and Pharmacokinetic Modeling 88 5.4.9.1 Guiding the Design of CDD Dosage Forms 88 5.4.9.2 Establishing In Vitro –In Vivo Correlation (IVIVC) 89 5.4.9.3 Physiologically Based Pharmacokinetic (PBPK) Modeling Tools 89 5.5 Conclusion 89 References 89 6 Mathematical Models Describing Kinetics Associated with Controlled Drug Delivery Across Membranes 95<br /> Annette L. Bunge 6.1 Introduction 95 6.1.1 General Description 95 6.1.2 Governing Equations 98 6.1.2.1 Differential Equations 98 6.1.2.2 Dimensionless Differential Equations 98 6.1.2.3 Initial and Boundary Conditions 99 6.1.3 Other Derived Quantities 100 6.1.4 Dimensionless Variables and Groups 102 6.2 Model Solutions 104 6.2.1 Type A Models –Well-Stirred Vehicle on One Membrane 104 6.2.1.1 Model A1 104 6.2.1.2 Model A2 107 6.2.1.3 Model A3 112 6.2.1.4 Model A4 116 6.2.1.5 Model A5 120 6.2.1.6 Model A6 121 6.2.1.7 Model A7 123 6.2.1.8 Model A8 124 6.2.1.9 Model A9 125 6.2.1.10 Model A9a 128 6.2.1.11 Model A9b 130 6.2.1.12 Model A10 132 6.2.1.13 Model A11 136 6.2.1.14 Model A12 137 6.2.1.15 Model A13 138 6.2.2 Type B Models – Unstirred Semi-infinite Vehicle on One Membrane 140 6.2.2.1 Model B1 140 6.2.2.2 Model B2 143 6.2.3 Type C –Well Stirred Vehicle on Two Membranes 145 6.2.3.1 Model C1 145 6.3 Solution Methods 149 6.3.1 Separation of Variables Solutions 150 6.3.1.1 Separating the Partial Differential Equation of N Independent Variables into N Ordinary Differential Equations 150 6.3.1.2 Choosing the Sign (Positive or Negative) on the Separation Constant 151 6.3.1.3 Finding the Constants of Integration and the Eigenvalues 152 6.3.1.4 Superposition 153 6.3.1.5 Finding the Remaining Constants of Integration 153 6.3.1.6 Guidelines for Using Separation of Variable Methods to Solve Partial Differential Equations 155 6.3.1.7 Methods for Making a Nonhomogeneous Partial Differential Equation or Nonhomogeneous Boundary Conditions Homogeneous 156 6.3.1.8 Choosing the Index Starting Value on the Sum of All Solutions (i.e. should n = 1 or 0?) 158 6.3.2 Laplace Transform Solutions 159 6.3.2.1 Using Laplace Transforms to Determine Lag Times, Steady-state Values and Other Derived Quantities 159 6.3.2.2 Inversion of Laplace Transformed Functions to Time Domain Functions by Method of Residues 161 6.3.2.3 Example A – Model A1 161 6.3.2.4 Example B – Model A10 165 6.3.3 Useful Identities 169 References 169 7 Understanding Drug Delivery Outcomes: Progress in Microscopic Modeling of Skin Barrier Property, Permeation Pathway, Dermatopharmacokinetics, and Bioavailability 171; Guoping Lian, Tao Chen, Panayiotis Kattou, Senpei Yang, Linyi Li, and Lujia Han 7.1 Introduction 171 7.2 Governing Equation 172 7.2.1 Homogenized Model 172 7.2.2 Microscopic Model 174 7.2.2.1 Solute Diffusion in SC Lipid 174 7.2.2.2 Solute Diffusion in SC Corneocytes 175 7.2.2.3 Solute Diffusion in Appendages 175 7.2.3 Numerical Methods 175 7.3 Input Parameters 176 7.3.1 SC Microstructure 176 7.3.2 SC Lipid–Water Partition 177 7.3.3 Diffusivity in SC Lipids 177 7.3.4 Binding to Keratin 179 7.3.5 Diffusivity in Corneocytes 181 7.3.6 Solute Diffusivity and Partition in Sebum 181 7.4 Application 183 7.4.1 Steady-State 183 7.4.2 Dermatopharmacokinetics 184 7.4.3 Systemic Pharmacokinetics 184 7.4.4 Shunt Pathway 185 7.5 Perspective 186 References 188 8 Role of Membrane Transporters in Drug Disposition 193<br
• Edition: 1st
• Publisher Details: Wiley
• Publication Date: 2021
• Extent: 1 online resource (576 pages)
• Languages: English
• ISBNs: 9781119769675
• 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.