Drug Stability and Chemical Kinetics

Preface
Acknowledgements
Contents
About the Editors
1: Principles of Pharmaceutical Analysis in Drug Stability and Chemical Kinetics
1.1 Introduction
1.2 Drug Stability
1.3 General Objectives of Drug Stability
1.4 Types of Drug Stability
1.4.1 Physical Stability
1.4.2 Chemical Stability
1.4.3 Microbiological Stability
1.5 Analytical Techniques
1.6 Kinetic Methods of Analysis
1.7 Protocol for Stability Studies
1.8 Routes of Drug Degradation
1.8.1 Physical Degradation
1.8.2 Crystallization of Amorphous Drugs
1.8.3 Transitions in Crystalline States
1.8.4 Moisture Adsorption
1.8.5 Vaporizing
1.8.6 Formation and Growth of Crystals
1.8.7 Chemical Routes of Drug Degradation
1.8.8 Solvolysis
1.8.9 Oxidation
1.8.10 Photolysis
1.8.11 Dehydration
1.8.12 Racemization
1.8.13 Incompatibilities
1.9 Chemical Kinetics
1.9.1 Rate of Order of Reactions
1.9.2 Expression of Rate Equation
1.9.3 Order of Reaction
1.9.4 Simple Order Kinetics
1.9.5 Zero Order of Reaction
1.9.6 First-Order Reaction
1.9.7 Second-Order Reaction
1.9.8 Complex Reactions
1.9.9 Reversible Reactions
1.9.10 Parallel Reactions
1.9.11 Consecutive Reactions
1.10 Factors Affecting the Stability of Drug
1.10.1 Temperature
1.10.2 Light
1.10.3 pH
1.10.4 Concentration
1.10.5 Moisture
1.10.6 Water
1.11 Conclusion
References
2: Guidelines for Drug Stability and Stability Testing
2.1 Introduction
2.2 Stability Testing Methods
2.2.1 Real-Time Stability Test
2.2.2 Accelerated Stability Tests
2.2.3 Retained Sample Stability Test
2.2.4 Cyclic Temperature Stress Testing
2.3 Stability Studies and Their Types
2.3.1 Physical Stability Studies
2.3.2 Chemical Stability Studies
2.3.3 Microbiological Stability Testing
2.4 Storage Conditions
2.5 ICH Guidelines
2.6 WHO Guidelines
2.7 Importance of Stability Studies
2.8 Conclusion
References
3: Chemical Kinetics and Its Applications in Drug Stability
3.1 Introduction
3.2 Rate of Reaction
3.2.1 Types of Rate of Reactions
3.2.1.1 Fast Reaction Rates
3.2.1.2 Measuring Fast Reactions
3.2.1.3 Slow Reaction Rates
3.2.1.4 Measuring Slow Reactions
3.3 Factors That Affect the Reaction Rate
3.3.1 Physical Factors
3.3.1.1 Surface Area
3.3.1.2 Concentration of Reactants
3.3.2 Chemical Factors
3.3.2.1 Temperature
3.3.2.2 pH
3.4 Applications of Chemical Kinetics in Drug Stability
3.4.1 Stability of Drug Products
3.4.2 Pharmacokinetics of Drug
3.4.3 Dissolution of a Drug
3.4.4 Chemical Kinetics and Drug Stability
3.4.5 Chemical Degradation Pathways of Pharmaceutical Drug Product
3.4.5.1 Photodegradation
3.4.5.2 Oxidation
3.4.5.3 Nucleophilic/Electrophilic Process
3.4.5.4 Electron Transfer Process
3.4.5.5 Autoxidation
3.4.5.6 Elimination
3.4.5.7 Decarboxylation
3.4.5.8 Hydrolysis
3.4.6 Physical Degradation of Pharmaceutical Drug Product
3.4.6.1 Polymorphism
3.4.6.2 Efflorescence
3.4.6.3 Adsorption
3.4.6.4 Hygroscopy
3.4.6.5 Vaporization
3.4.6.6 Aging
3.4.7 Microbiological Degradation of Pharmaceutical Drug Product
3.5 Conclusion
References
4: Methods and Protocols for Drug Stability Studies
4.1 Introduction
4.2 Importance of Conducting Drug Stability Studies
4.3 Types of Drug Stabilities
4.3.1 Physical Stability
4.3.2 Chemical Stability
4.3.3 Microbiological Stability
4.3.4 Therapeutic Stability
4.3.5 Toxicological Stability
4.4 Methods for the Stability Studies of Drugs
4.4.1 Real-Time Stability Testing
4.4.2 Accelerated Stability Testing
4.4.3 Retained Sample Stability Testing
4.4.4 Cyclic Temperature Stress Testing
4.5 Protocol of Drug Stability Testing
4.5.1 Number of Batches
4.5.2 Containers and Closures
4.5.3 Orientation of Storage of Containers
4.5.4 Sampling Time Points
4.5.5 Test Storage Conditions
4.5.6 Mean Kinetic Temperature
4.5.7 Test Parameters
4.6 Stability Test Equipment
4.7 Climate Zones
4.8 Applications of Stability Studies
4.8.1 For Drug Development
4.8.2 For Approval from Regulatory Bodies
4.8.3 Post-Registration Period
4.9 Conclusion
References
5: Physical Basis of Degradation of Pharmaceutical Products
5.1 Degradation and Stability of Pharmaceutical Products
5.2 Factors Affecting Stability of Pharmaceutical Products
5.3 Types of Stability
5.3.1 Chemical Stability
5.3.2 Photostability
5.3.3 Physical Stability
5.3.4 Solid-State Stability
5.3.5 Microbial Stability
5.4 Physical Basis Affecting Stability of Pharmaceutical Products
5.4.1 Temperature
5.4.2 Ionic Strength
5.4.3 Acid and Base Catalysis (pH)
5.4.4 Solvent
5.4.5 Light
5.4.6 Oxygen
5.4.7 Particle Size Distribution
5.4.8 Moisture
5.5 Possible Effects of Physical Instability
5.6 Stability of Drugs in Pharmaceutical Products
5.7 Stability of Excipients Used in Pharmaceutical Products
5.8 Kinetic Parameters of Physical Degradation
5.9 Methods for Detecting Physical Degradation
5.10 Conclusion
References
6: Role of Microbial Degradation on Drug Stability
6.1 Introduction
6.2 Factors Affecting Drug Stability
6.2.1 Light (Photolysis)
6.2.2 Temperature
6.2.3 Moisture
6.3 Containers and Closures
6.3.1 Glass
6.3.2 Plastic
6.3.3 Metals
6.3.4 Rubber
6.4 Types of Drug Degradation
6.4.1 Physical Degradation
6.4.2 Polymorphic Changes
6.4.3 Loss of Volatile Components
6.4.4 Loss of Water
6.4.5 Examples
6.4.6 Color Changes
6.4.7 Absorption of Water
6.4.8 Chemical Degradation
6.4.9 Hydrolysis
6.4.10 Oxidation
6.4.11 Decarboxylation
6.4.12 Isomerization
6.4.13 Polymerization
6.4.14 Photodegradation
6.4.15 Microbiological Degradation
6.4.16 Sources of Microbiological Contamination
6.5 Microorganisms in Manufacturing Sites
6.5.1 Microorganisms in Clean Room
6.5.2 Microorganisms in Raw Materials
6.5.3 Microorganisms in Pharmaceutical Products
6.5.3.1 Pharmacy Stores
6.5.3.2 Hospitals
6.6 Role of Microbiological Contamination
6.6.1 Change of Activity
6.6.2 Acetylsalicylic Acid
6.6.3 Caffeine
6.6.4 Hydrocortisone
6.6.5 Progesterone
6.6.6 Atropine
6.6.7 Visible Effect
6.6.8 Visible Growth
6.6.9 Loss of Consistency
6.6.10 Separation of Phases
6.7 Approaches to Counter Microbial Instability
6.7.1 Use of Silver Nanoparticles
6.7.2 Increase in Paraben Efficacy
6.7.3 Use of Zinc Oxide
6.8 Conclusion
References
7: Role of Decomposition on Drug Stability
7.1 Introduction
7.2 Types of Stability
7.2.1 Physical Stability
7.2.2 Chemical Stability
7.2.3 Microbiological Stability
7.2.4 Therapeutic Stability
7.2.5 Toxicological Stability
7.3 Factors Affecting Drug Stability
7.3.1 Temperature
7.3.2 pH
7.3.3 Moisture
7.3.4 Light
7.3.5 Concentration
7.3.6 Pharmaceutical Dosage Form
7.3.7 Drug Incompatibility
7.3.8 Oxygen
7.4 Types of Degradation Reactions
7.4.1 Physical Degradation Reactions
7.4.1.1 Loss of Water
7.4.1.2 Loss of Volatile Components
7.4.1.3 Polymorphic Changes
7.4.1.4 Crystal Growth
7.4.1.5 Colour Changes
7.4.1.6 Absorption of Water
7.4.2 Chemical Degradation Reactions
7.4.2.1 Hydrolysis
7.4.2.2 Oxidation
7.4.2.3 Decarboxylation
7.4.2.4 Elimination
7.4.2.5 Isomerization
7.4.2.6 Dimerization
7.4.2.7 Epimerization
7.4.2.8 Photodegradation
7.4.2.9 Dehydration
7.5 Compatibility of Drug with Packaging Material
7.5.1 Glass
7.5.2 Plastic
7.5.3 Rubber
7.5.4 Metal
7.6 Degradation Mechanisms in Pharmaceutical Dosages Forms
7.6.1 Oral Dosage Form
7.6.1.1 Problem
7.6.1.2 Prevention
7.6.2 Parenteral
7.6.2.1 Problem
7.6.2.2 Prevention
7.6.3 Emulsions
7.6.3.1 Problem
7.6.3.2 Prevention
7.7 Role of Pharmacist
7.8 Conclusions
References
8: Role of Catalysis and Catalytic Agents in Drug Stability
8.1 Introduction
8.1.1 Unit of Catalytic Activity
8.2 Working Principle
8.3 Reaction Energetics
8.4 Types of Catalysis
8.4.1 Heterogeneous Catalysis
8.4.2 Homogeneous Catalysis
8.4.3 General Acid and Base Catalysis (Ester Hydrolysis)
8.4.4 Other Types of Catalysis
8.4.5 Photocatalysis
8.4.6 Biocatalysis
8.4.7 Nanocatalysis
8.4.8 Tandem Catalysis
8.4.9 Autocatalysis
8.5 Importance of Catalytic Agents in Drug Discovery and Stability
8.5.1 Challenges in Drug Discovery
8.6 Role of Catalysts
8.6.1 Catalytic Role of Metal Ions
8.6.2 Organometallics Catalysis
8.7 Factors Affecting Stability
8.7.1 Effect of pH
8.7.2 Effect of Concentration
8.7.3 Effect of Ionic Strength
8.7.4 Effect of Co-solvents
8.7.5 Effects of Protein Binding
8.7.6 Effect of Light
8.7.7 Effect of Temperature
8.7.8 Hydrolysis
8.7.9 Oxidation
8.7.10 Effect of Catalytic Agents on Drug Stability
8.7.11 Inorganic Catalysts/Synthetic Catalysts
8.7.12 Organic Catalysts/Natural Catalysts
8.8 Conclusion
References
9: Analytical Techniques for the Assessment of Drug Stability
9.1 Introduction
9.2 Drug Stability
9.3 Importance of Drug Stability Studies
9.4 Types of Drug Stabilities
9.4.1 Physical Stability
9.4.2 Chemical Stability
9.4.3 Microbiological Stability
9.4.4 Therapeutic Stability
9.4.5 Toxicological Stability
9.5 Types of Stability Studies
9.5.1 Long Term Stability
9.5.2 Intermediate Stability
9.5.3 Accelerated Testing
9.5.4 In-Use Stability
9.5.5 Role of the Analytical Techniques in Drug Stability
9.6 Role of Chemical Kinetics in Drug Stability Studies
9.7 Analytical Techniques
9.7.1 Titrimetric Techniques
9.7.2 Chromatography Techniques
9.7.2.1 Column Chromatography
9.7.2.2 Gas Chromatography
9.7.2.3 High-Performance Thin-Layer Chromatography
9.7.2.4 High-Performance Liquid Chromatography
9.7.2.5 Thin-Layer Chromatography
9.7.3 Spectroscopic Techniques
9.7.3.1 Spectrophotometry
9.7.3.2 Near-Infrared Spectroscopy (NIRS)
9.7.3.3 Nuclear Magnetic Resonance Spectroscopy (NMRS)
9.7.3.4 Phosphorimetry and Fluorimetry
9.7.4 Electrochemical Methods
9.7.5 Kinetic Method of Analysis (KMA)
9.7.6 Electrophoretic Procedures
9.7.7 Flow Injection Analysis/Sequential Injection Analysis (FIA and SIA)
9.7.8 Hyphenated Techniques
9.7.9 Thermal Analytical Techniques
9.7.9.1 Differential Scanning Calorimetry (DSC)
9.7.9.2 Thermogravimetric Analysis (TGA)
9.8 Conclusion
References
10: Stability of Pharmaceutical Products
10.1 Introduction
10.2 Significance of Studying the Stability of Drug Products
10.3 Factors Affecting the Stability of Pharmaceutical Products
10.3.1 Moisture
10.3.2 Excipients
10.3.3 Temperature
10.3.4 pH
10.3.5 Oxygen
10.3.6 Light
10.4 Types of Stability of Pharmaceutical Products
10.5 Classification of Pharmaceutical Products with Respect to Stability Studies
10.6 Stability Evaluation Studies
10.6.1 Real-Time Stability Testing
10.6.2 Accelerated Stability Testing
10.6.3 Retained Sample Stability Testing
10.6.4 Cyclic Temperature Stress Testing
10.7 Advantages of Stability Studies of Pharmaceutical Products
10.8 Disadvantages
10.9 Conclusion
References
11: Role of Kinetic Models in Drug Stability
11.1 Introduction
11.2 Types of Stability of Drugs
11.2.1 Physical Stability
11.2.2 Chemical Stability
11.2.3 Microbiological Stability
11.3 Kinetic Models
11.3.1 Zero-Order Kinetic Model
11.3.2 Role
11.3.3 First-Order Kinetic Model
11.3.4 Role
11.3.5 Higuchi Model
11.3.6 Role
11.3.7 Korsmeyer-Peppas Model
11.3.8 Role
11.3.9 Hixson-Crowell Model
11.3.10 Role
11.3.11 Merits and Demerits of Kinetic Models
11.4 Factors Influencing the Rate of Kinetics in Kinetic Models´ Selection
11.4.1 Mechanical Factors
11.4.2 Physical Factors
11.4.3 Relative Humidity
11.4.4 Effect of Solvent
11.4.5 pH
11.5 Conclusion
References
12: Stability Studies of Vaccines
12.1 Introduction
12.2 Immune System
12.2.1 Types of Immune Systems
12.2.2 Innate or General Immune System
12.2.3 Adaptive/Specific Immune System
12.2.4 Immunization and Its Types
12.2.5 History of Smallpox and Vaccine Development
12.3 Quality Control and Vaccine Development
12.3.1 Monitoring Efficacy of Vaccines (Pre-clinical Stage)
12.3.2 Assays for Measuring the Concentration and Integrity of Antigens
12.3.3 Assays for Measuring Biological Activity, Active Concentration, and Confirmation of Antigen
12.3.4 Monitoring Efficacy of Vaccines (Clinical Stage)
12.3.5 Adverse Events Following Immunization (AEFI)
12.3.6 Risk Factors Related with Vaccination
12.4 Vaccine Kinetics and Stability
12.4.1 Temperature Ramping Experiment
12.4.2 Accelerated Stability Studies
12.4.3 Kinetic Model (Zero or First Order)
12.4.4 Sophisticated Degradation Kinetic Models (Two-Step Model)
12.5 Conclusion
References
13: Stability Studies of Proteinous Compounds
13.1 Introduction
13.2 Essential and Nonessential Proteins
13.3 Protein Structures
13.3.1 Primary Structure
13.3.2 Secondary Structure
13.3.3 Tertiary Structure
13.3.4 Quaternary Structure
13.4 Domains of Protein
13.5 Classification of Proteins Based on Structure (SCOP)
13.5.1 Chemical Composition-Based Classification of Protein
13.5.2 Simple Proteins
13.5.3 Conjugated Proteins
13.5.4 Phosphoproteins
13.5.5 Glycoproteins
13.5.6 Chromoproteins
13.5.7 Classification of Proteins According to Shape
13.5.7.1 Fibrous Proteins
13.5.7.2 Fibroin
13.5.7.3 Collagen
13.5.7.4 α-Keratins
13.5.7.5 Elastin
13.5.7.6 Globular Proteins
13.5.8 Classification of Proteins According to Solubility
13.5.8.1 Globular Proteins
13.5.8.2 Fibrous Proteins
13.5.9 Protein Classification Based on Functions
13.5.9.1 Hormonal Protein
13.5.9.2 Enzymatic Protein
13.5.9.3 Structural Protein
13.5.9.4 Defensive Protein
13.5.9.5 Storage Protein
13.5.9.6 Transport Protein
13.5.9.7 Respiratory Protein
13.5.9.8 Receptor Protein
13.5.9.9 Contractile Protein
13.6 Stability of Proteins
13.7 Types of Stability
13.7.1 Stability: An Important Precondition for Crystallization
13.7.2 Compositional Stability
13.7.3 Conformational Stability
13.7.4 Structure Level Stability of the Proteins
13.7.4.1 Primary Structure
13.7.4.2 Secondary Structure
13.7.4.3 Tertiary Structure
13.7.4.4 Quaternary Structure
13.8 Factors Affecting Protein Stability
13.8.1 Temperature
13.8.2 Freeze-Thaw
13.8.3 Physical Factors
13.8.4 Oxidation
13.8.5 Heavy Metals
13.8.6 Microbial Growth
13.8.7 Proteases
13.8.8 Denaturation
13.8.9 Chemical Denaturation
13.8.10 Pressure-Induced Denaturation
13.8.11 Solid State Denaturation
13.8.12 Intrinsically Denatured Proteins
13.9 Limitations for Stability Studies
13.10 Chemical Kinetics
13.10.1 History of Chemical Kinetics
13.10.2 Rate of Reaction
13.10.3 Order of Reaction
13.10.4 Molecularity of Reaction
13.10.5 Types of Chemical Reactions
13.10.5.1 Instantaneous Reactions
13.10.5.2 Slow Reactions
13.10.5.3 Moderate Reactions
13.10.5.4 Fast Reactions
13.11 Factors Affecting the Reaction Rate
13.11.1 Physical State
13.11.2 Surface Area of Solid State
13.11.3 Concentration
13.11.4 Temperature
13.11.5 Catalysts
13.11.6 Pressure
13.11.7 Absorption of Light
13.11.8 Free Energy
13.11.9 Stability Testing
13.12 Need and Purpose of Guidelines for Stability Studies
13.12.1 Brief History
13.12.2 Guidelines by the Food and Drug Administration
13.12.3 Benefits of Regulatory Harmonization
13.12.4 ICH Guidelines
13.12.5 General Categories of ICH Guidance
13.12.6 ``Q´´ Guidance
13.12.7 ``S´´ Guidance
13.12.8 ``E´´ Guidance
13.12.9 ``M´´ Guidance
13.13 Guidelines for Stability Studies
13.13.1 ICH and FDA Stability Regulatory Guidelines
13.13.2 Guidelines
13.13.3 Q1A
13.13.4 Q1B
13.13.5 Q1C
13.13.6 Q1D
13.13.7 Q1E
13.13.8 Q5C
13.13.9 ICH Q1AR2
13.14 CPMP Stability Guidelines
13.14.1 Guidance CPMP/QWP/122/02
13.14.2 Guidance CPMP/QWP/576/96
13.14.3 Guidance CPMP/QWP/2934/99
13.14.4 Guidance CPMP/QWP/159/96
13.14.5 Guidance CPMP/QWP/609/96
13.14.6 Guidance CPMP/QWP/072/96
13.15 WHO Stability Guidelines
13.16 Stability of Climatic Zones
13.16.1 Mean Kinetic Temperature
13.17 Importance of Protein Stability
13.17.1 Chemical Instability
13.17.2 Physical Instability
13.17.3 Denaturation
13.17.4 Aggregation
13.17.5 Precipitation
13.17.6 Surface Adsorption
13.17.7 Improving Protein Stability
13.18 Chemical Kinetics of Proteinous Compounds
13.19 Applications and Advantages of Stability Studies
13.20 Role of Pharmacists in Protein Stability
13.21 Conclusion
References
14: Stability Studies of Extemporaneous Pharmaceutical Products
14.1 Extemporaneous Pharmaceutical Products
14.2 Need of Extemporaneous Preparations
14.3 Compounding Standards for Extemporaneous Preparations
14.4 Commonly Compounded Extemporaneous Products
14.5 Current Scenario of Extemporaneous Pharmaceutical Products
14.6 Stability Studies: An Introduction
14.7 Importance of Stability Studies
14.8 General Protocol for Conducting Stability Studies
14.9 Stability of Extemporaneous Pharmaceutical Products
14.9.1 Solutions
14.9.2 Suspension
14.9.3 Ointments
14.9.4 Tablets
14.10 Stability Criteria and Beyond-Use Dating
14.11 Conclusion
References
15: Stability Studies of Parenteral Products
15.1 What Are Parenteral Products?
15.2 Why We Formulate These Products and What Are the Limitations?
15.3 Types of Parenteral Products
15.3.1 Injections
15.3.2 Infusions
15.3.3 Concentrates for Injections or Infusions
15.3.4 Powders for Injections or Infusions
15.3.5 Implants
15.4 Stability Issues
15.5 Stability Evaluation
15.6 Stability Testing
15.7 Chemical Kinetics Involved in the Stability Issues
15.7.1 Factors Affecting the Stability of the Parenteral Products
15.7.2 External Factors
15.7.3 Internal Factors
15.7.4 Standards and Guidelines for Stability Study of Parenteral Products
15.7.5 ICH Q1A: Stability Testing of New Drug Substances and Products
15.7.6 Q1B: Photostability Testing
15.7.7 Q1C: Stability Testing for New Dosage Forms
15.7.8 Q1D: Bracketing and Matrixing
15.7.9 Q1E: Evaluation of Stability Data
15.7.10 Q5C: Stability Testing of Biotech Products
15.8 Guidelines
15.8.1 Drug Substance
15.8.2 Stress Testing
15.8.3 Batch Selection
15.8.4 Container-Closure System
15.8.5 Specifications
15.8.6 Testing Frequency
15.8.7 Storage Conditions
15.8.8 Stability Commitment
15.8.9 Data Evaluation
15.8.10 Labeling
15.8.11 Other ICH Guidelines
15.8.11.1 Drug Product
15.8.11.2 Photostability Testing
15.8.11.3 Selection of Batches
15.8.11.4 Container-Closure System
15.8.11.5 Specification
15.8.11.6 Testing Frequency
15.8.11.7 Storage Conditions
15.8.11.8 Stability Commitment
15.8.11.9 Evaluation
15.8.11.10 Labeling
15.8.12 Analytical Techniques for Stability Studies of Parenteral Products
15.8.13 Advantages of Analytical Techniques
15.8.14 Disadvantages of Analytical Techniques
15.9 Conclusion
References
16: Stability Studies of Solid Dosage Forms
16.1 Introduction
16.2 Types of Solid Dosage Form
16.2.1 Powders and Granules
16.2.2 Capsules
16.2.3 Tablets
16.2.4 Solid Oral-Modified Release Dosage Forms and Drug Delivery System
16.3 Stability, Their Types, and Factors Affecting Stability of Solid Dosage Forms
16.3.1 Stability
16.3.2 Physical Stability
16.3.3 Visual Evaluation
16.3.4 Sub-visual Evaluation
16.3.5 Chemical Evaluation
16.3.6 Degradation Methods
16.3.7 General Tests
16.3.8 Methods for Evaluation of Chemical Instability
16.3.9 Microbiological Stability
16.3.10 Factors Affecting Stability Studies
16.3.10.1 Temperature
16.3.10.2 pH
16.3.10.3 Moisture
16.3.10.4 Light
16.3.10.5 Oxygen
16.4 Limitations of Stability Studies
16.5 Chemical Kinetics Involved, Their Types, and Factors Affecting the Chemical Kinetics
16.5.1 Reaction Rate
16.5.2 Rate Law
16.5.3 Apparent or Pseudo-Order Reaction
16.5.4 Zero-Order Reactions
16.5.5 First-Order Reaction
16.5.6 Second-Order Reactions
16.5.7 Chemical Kinetics
16.5.8 Types of Chemical Kinetics
16.5.8.1 Very Fast or Instantaneous Reaction
16.5.8.2 Moderate Reaction
16.5.8.3 Very Slow Reactions
16.5.9 Factors Affecting Chemical Kinetics
16.5.9.1 Concentration of Reactants
16.5.9.2 Surface Area and Medium of Reactants
16.5.9.3 Temperature
16.5.9.4 Presence of a Catalyst
16.5.9.5 Pressure
16.5.9.6 Mixing
16.6 Guidelines (Like FDA and ICH) for Stability Studies and Chemical Kinetics
16.6.1 General Guidelines for Stability Studies
16.6.2 Stress Testing
16.6.3 Climate Zone for Stability Testing
16.6.4 Selection of Batches
16.6.5 Container and Closure System
16.6.6 Specifications
16.6.7 Test Frequency
16.6.8 Storage Conditions
16.7 Why We Perform Stability Studies for Solid Dosage Forms
16.8 Why We Study the Chemical Kinetics in Stability Studies of Solid Dosage Forms
16.8.1 Half-Life
16.8.2 Shelf Life (t0.9)
16.9 Pharmaceutical Instability Due to Variation in Chemical Kinetics
16.10 Applications of Stability Studies, Chemical Kinetics, and Their Advantages and Disadvantages
16.10.1 Applications of Stability Studies
16.10.2 Stability Issues
16.10.3 Applications of Chemical Kinetic Studies
16.11 Role of Pharmacist in Overall Stability Studies and Chemical Kinetics of Solid Dosage Forms
16.12 Conclusion
References