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Biopharmaceutics Modeling and Simulations Theory, Practice, Methods, and Applications

ISBN-10: 1118028686

ISBN-13: 9781118028681

Edition: 2012

Authors: Kiyohiko Sugano

List price: $195.95
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Description:

This book explains the basics of modeling and simulations programs, how they work and are applied for different biopharmaceutical properties, and their applications in drug development. The author offers a valuable guide to the design of drug formulations for achieving desired medicinal effects, featuring practical application examples in drug research. Using illustrations and practice problems rather than heavy math, the applications covered include running and interpreting models, compound and formulation selection, mechanisms, and virtual clinical trials. This useful text will guide pharmaceutical professionals in the tools and practices of modeling biopharmaceutics.
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Book details

List price: $195.95
Copyright year: 2012
Publisher: John Wiley & Sons, Incorporated
Publication date: 8/10/2012
Binding: Hardcover
Pages: 520
Size: 6.50" wide x 9.50" long x 1.25" tall
Weight: 1.848
Language: English

Preface
List of Abbreviations
Introduction
An Illustrative Description of Oral Drug Absorption: The Whole Story
Three Regimes of Oral Drug Absorption
Physiology of the Stomach, Small Intestine, and Colon
Drug and API Form
Undissociable and Free Acid Drugs
Free Base Drugs
Salt Form Cases
The Concept of Mechanistic Modeling
References
Theoretical Framework I: Solubility
Definition of Concentration
Total Concentration
Dissolved Drug Concentration
Effective Concentration
Acid-Base and Bile-Micelle-Binding Equilibriums
Monoprotic Acid and Base
Multivalent Cases
Bile-Micelle Partitioning
Modified Henderson-Hasselbalch Equation
Kbm from Log Poct
Equilibrium Solubility
Definition of Equilibrium Solubility
pH-Solubility Profile (pH-Controlled Region)
Solubility in a Biorelevant Media with Bile Micelles (pH-Controlled Region)
Estimation of Unbound Fraction from the Solubilities with and without Bile Micelles
Common Ionic Effect
Important Conclusion from the pH-Equilibrium Solubility Profile Theory
Yalkowsky's General Solubility Equation
Solubility Increase by Converting to an Amorphous Form
Solubility Increase by Particle Size Reduction (Nanoparticles)
Cocrystal
References
Theoretical Framework II: Dissolution
Diffusion Coefficient
Monomer
Bile Micelles
Effective Diffusion Coefficient
Dissolution and Particle Growth
Mass Transfer Equations: Pharmaceutical Science Versus Fluid Dynamics
Dissolution Equation with a Lump Sum Dissolution Rate Coefficient (kdiss)
Particle Size and Surface Area
Monodispersed Particles
Polydispersed Particles
Diffusion Layer Thickness I: Fluid Dynamic Model
Reynolds and Sherwood Numbers
Disk (Levich Equation)
Tube (Graetz Problem)
Particle Fixed to Space (Ranz-Marshall Equation)
Floating Particle
Nonspherical Particle
Minimum Agitation Speed for Complete Suspension
Other Factors
Diffusion Layer Thickness II: Empirical Models for Particles
Solid Surface pH and Solubility
Nucleation
General Description of Nucleation and Precipitation Process
Classical Nucleation Theory
Concept of Classical Nucleation Theory
Mathematical Expressions
Application of a Nucleation Theory for Biopharmaceutical Modeling
References
Theoretical Framework III: Biological Membrane Permeation
Overall Scheme
General Permeation Equation
Permeation Rate Constant, Permeation Clearance, and Permeability
Intestinal Tube Flatness and Permeation Parameters
Effective Concentration for Intestinal Membrane Permeability
Effective Concentration for Unstirred Water Layer Permeation
Effective Concentration for Epithelial Membrane Permeation: the Free Fraction Theory
Surface Area Expansion by Plicate and Villi
Unstirred Water Layer Permeability
Basic Case
Particles in the UWL (Particle Drifting Effect)
Epithelial Membrane Permeability (Passive Processes)
Passive Transcellular Membrane Permeability: pH Partition Theory
Intrinsic Passive Transcellular Permeability
Solubility-Diffusion Model
Flip-Flop Model
Relationship between Ptrans,0 and log Poct
Paracellular Pathway
Relationship between log Doct, MW, and Fa%
Enteric Cell Model
Definition of Papp
Enzymatic Reaction: Michaelis-Menten Equation
First-Order Case 1: No Transporter and Metabolic Enzymes
First-Order Case 2: Efflux Transporter in Apical Membrane
Apical Efflux Transporter with Km and Vmax
Apical Influx Transporter with Km and Vmax
UWL and Transporter
No Transporter
Influx Transporter and UWL
Efflux Transporter
Gut Wall Metabolism
The Qgut Model
Simple Fg Models
Theoretical Consideration on Fg
Derivation of the Fg Models
Derivation of the Anatomical Fg Model
Interplay between CYP3A4 and P-gp
Hepatic Metabolism and Excretion
References
Theoretical Framework IV: Gastrointestinal Transit Models and Integration
GI Transit Models
One-Compartment Model/Plug Flow Model
Plug Flow Model
Three-Compartment Model
S1I7CX (X = 1-4) Compartment Models
Convection-Dispersion Model
Tapered Tube Model
Time-Dependent Changes of Physiological Parameters
Gastric Emptying
Water Mass Balance
Bile Concentration
Integration 1: Analytical Solutions
Dissolution Under Sink Condition
Monodispersed Particles
Polydispersed Particles
Fraction of a Dose Absorbed (Fa%)
Approximate Fa% Analytical Solutions 1: Case-by-Case Solution
Permeability-Limited Case
Solubility-Permeability-Limited Case
Dissolution-Rate-Limited Case
Approximate Fa% Analytical Solutions 2: Semi-General Equations
Sequential First-Order Kinetics of Dissolution and Permeation
Minimum Fa% Model
Approximate Fa% Analytical Solutions 3: FaSS Equation
Application Range
Derivation of Fa Number Equation
Refinement of the FaSS Equation
Advantage of FaSS Equation
Limitation of FaSS Equation
Interpretations of Fa Equations
Approximate Analytical Solution for Oral PK Model
Integration 2: Numerical Integration
Virtual Particle Bins
The Mass Balance of Dissolved Drug Amount in Each GI Position
Controlled Release of Virtual Particle Bin
In Vivo FA From PK Data
Absolute Bioavailability and Fa
Relative Bioavailability Between Solid and Solution Formulations
Relative Bioavailability Between Low and High Dose
Convolution and Deconvolution
Convolution
Deconvolution
Other Administration Routes
Skin
References
Physiology Of Gastrointestinal Tract And Other Administration Sites In Humans and Animals
Morphology of Gastrointestinal Tract
Length and Tube Radius
Surface Area
Small Intestine
Colon
Degree of Flatness
Small Intestine
Colon
Epithelial Cells
Apical and Basolateral Lipid Bilayer Membranes
Tight Junction
Mucous Layer
Movement of the Gastrointestinal Tract
Transit Time
Gastric Emptying Time (GET)
Small Intestinal Transit Time
Colon Transit Time
Migrating Motor Complex
Agitation
Mixing Pattern
Agitation Strength
Unstirred Water Layer on the Intestinal Wall
Fluid Character of the Gastrointestinal Tract
Volume
Stomach
Small Intestine
Colon
Bulk Fluid pH and Buffer Concentration
Stomach
Small Intestine
Colon
Microclimate pH
Small Intestine
Colon
Bile Micelles
Stomach
Small Intestine
Colon
Enzymes and Bacteria
Viscosity, Osmolality, and Surface Tension
Transporters and Drug-Metabolizing Enzymes in the Intestine
Absorptive Drug Transporters
PEP-T1
OATP
Efflux Drug Transporters
P-gp
Drug-Metabolizing Enzymes
CYP3A4
Glucuronyl Transferase and Sulfotransferase
Intestinal and Liver Blood Flow
Absorption Sites Connected to Portal Vein
Villous Blood Flow (Qvilli)
Hepatic Blood Flow (Qh)
Physiology Related to Enterohepatic Recirculation
Bile Secretion
Mass Transfer into/from the Hepatocyte
Sinusoidal Membrane (Blood to Hepatocyte)
Canalicular Membrane (Hepatocyte to Bile Duct)
Nasal
Pulmonary
Fluid in the Lung
Mucociliary Clearance
Absorption into the Circulation
Skin
References
Drug Parameters
Dissociation Constant (pKa)
pH Titration
pH-UV Shift
Capillary Electrophoresis
pH-Solubility Profile
Calculation from Chemical Structure
Recommendation
Octanol-Water Partition Coefficient
Shake Flask Method
HPLC Method
Two-Phase Titration Method
PAMPA-Based Method
In Silico Method
Recommendation
Bile Micelle Partition Coefficient (Kbm)
Calculation from Solubility in Biorelevant Media
Spectroscopic Method
Recommendations
Particle Size and Shape
Microscope
Laser Diffraction
Dynamic Laser Scattering (DLS)
Recommendations
Solid Form
Nomenclature
Crystalline and Amorphous
Salts, Cocrystals, and Solvates
Hydrate
Crystal Polymorph
True Polymorph and Pseudopolymorph
Kinetic Resolution versus Stable Form
Dissolution Profile Advantages of Less Stable Forms
Enantiotropy
Solid Form Characterization
Polarized Light Microscopy (PLM)