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Rational Design of Stable Protein Formulations Theory and Practice

ISBN-10: 0306467410

ISBN-13: 9780306467417

Edition: 2002

Authors: John F. Carpenter, Mark C. Manning

List price: $249.99
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Description:

Recombinant proteins and polypeptides continue to be the most important class of biotechnology-derived agents in today's pharmaceutical industry. Over the past few years, our fundamental understanding of how proteins degrade and how stabilizing agents work has made it possible to approach formulation of protein pharmaceuticals from a much more rational point of view. This book describes the current level of understanding of protein instability and the strategies for stabilizing proteins under a variety of stressful conditions.
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Book details

List price: $249.99
Copyright year: 2002
Publisher: Springer
Publication date: 4/30/2002
Binding: Hardcover
Pages: 206
Size: 6.00" wide x 9.00" long x 0.75" tall
Weight: 0.946
Language: English

Practical Approaches to Protein Formulation Development
Introduction
Preparation for Formulation Development
Resource Requirements for Formulation Development
Useful Information for Designing Formulations
Preformulation Development
Characterization of Protein Pharmaceuticals
Accelerated Stability Studies
Developmentof Analytical Methods
Evaluation of the Significance of Problems
Formulation Development
Formulation Options for Protein Pharmaceuticals
Typical Protein Stability Problems: Causes and Solutions
Optimization of Formulation Variables
Necessary Studies for Formulation Development
Strategies to Overcome Difficult Formulation Problems
Formulation in Commercial Product Development
Critical Formulation Decisions During Pharmaceutical Development
Formulation for Early Preclinical and Clinical Studies
Commercial Formulation
Regulatory Issues in Formulation Development
List of Regulatory Documents
References
Recombinant Production of Native Proteins from Escherichia coli
Introduction
Distribution of Expressed Proteins
Cell Washing and Lysis
Purification of Soluble, Folded Proteins
Purification and Refolding of Soluble, Misfolded Proteins
Purification and Refolding of Proteins from Inclusion Bodies
Washing and Solubilization of Inclusion Bodies
Purification of Expressed Proteins from Inclusion Bodies
Refolding Mechanism
Disulfide Bond Formation
Removal of Denaturant
Effects of Tag Sequences
Effects of Excipients
Response Surface Methodology
High Pressure Disaggregation and Refolding
Methods to Analyze Folded Structures
Bioactivity
Binding to Receptors
Dilsulfide Bond Analysis
Spectroscopy
Conformational Stability
Limited Proteolysis
References
Physical Stabilization of Proteins in Aqueous Solution
Introduction
Overview of Physical Stability
Thermodynamic Control of Protein Stability
Kinetic Control of Protein Stability
Interactions of Excipients with Proteins
Preferentially Excluded Cosolvents
Buffers/Salts
Specific Binding of Ligands
Protein Self-Stabilization
Physical Factors Affecting Protein Stability
Temperature
Freeze-Thawing
Agitation and Exposure to Denaturing Interfaces
Pressure
Conclusions
Derivation of the Wyman Linkage Function and Application to the Timasheff Preferential Exclusion Mechanism
References
Effects of Conformation on the Chemical Stability of Pharmaceutically Relevant Polypeptides
Introduction
Relationship Between Structure and Deamidation Rates
Primary Structure Effects
Secondary Structure Effects
Tertiary Structure Effects
Summary of Structure Effects on Deamidation
Role of Structure in Protein Oxidation
Types of Oxidation Processes
Effects of Oxidation of Surface and Buried Methionines on Protein Structure
Limiting Solvent Accessibility of Residues
Conformational Control of Oxidation in Aqueous Solution
Structural Control of Oxidation in Lyophilized Products
Summary of Structural Control of Oxidation
Summary
References
Rational Design of Stable Lyophilized Protein Formulations: Theory and Practice
Introduction
Minimal Criteria for a Successful Lyophilized Formulation
Inhibition of Lyophilization-Induced Protein Unfolding
Storage at Temperatures Below Formulation Glass Transition Temperature
The Water Content is Relatively Low
A Strong, Elegant Cake Structure is Obtained
Steps Taken to Minimzie Specific Routes of Protein Chemical Degradation
Rational Design of Stable Lyophiilized Formulations
Choice of Buffer
Specific Ligands/pH that Optimizes Thermodynamic Stability of Protein
Trehalose or Sucrose to Inhibit Protein Unfolding and Provide Glassy Matrix
Bulking Agent (e.g., Mannitol, Glycine or Hydroxyethyl Starch)
Nonionic Surfactant to Inhibit Aggregation
Acknowledgments
References
Spray-Drying of Proteins
Introduction: Why Spray-Dry a Protein?
Developments in the Last 10 Years
The Practice of Spray-Drying Proteins
Type of Equipment
Spray-Drying Conditions
Influence of Formulation
Pure Proteins
Formulated Systems
Use of Added Surface Active Substances
Concluding Remarks
References
Surfactant-Protein Interactions
Introduction
Proteins and Surfactants at Surfaces
Protein-Surfactant Interactions in Solution
Surfactant Effects on Protein Assembly State
Surfactant Effects on Proteins During Freezing, Freeze-Drying and Reconstitution
Enzymatic Degradation of Non-Ionic Surfactants
Recommendations for Protein Formulation
References
High Throughout Formulation: Strategies for Rapid Development of Stable Protein Products
Introduction
Overall Structure of the HTF Approach
Role of an Established Decision Tree for Formulation Design
Constraints on a Pharmaceutically Acceptable Protein Formulation
Proper Choice of Dosage Form
Preformulation Studies
Proper Choice of Excipients
Estimates of Resources Needed for Formulation Development
Use of Software and Databases to Assist in the HTF Process
Essential Analytical Methods
Stability Protocols
Unified Strategy for HTF
References
Index