Pharmaceutical Isothermal Calorimetry

3155fm......Page 1
Pharmaceutical Isothermal Calorimetry......Page 2
Dedication......Page 4
Preface......Page 5
Contents......Page 7
INTRODUCTION......Page 10
Table of Contents......Page 0
BRIEF HISTORY OF CALORIMETRY......Page 13
HEAT AS AN INDICATOR OF CHANGE......Page 15
INTRODUCTION TO THERMODYNAMICS......Page 17
First Law of Thermodynamics......Page 18
Second Law of Thermodynamics......Page 19
Helmholtz and Gibbs Functions......Page 20
Nomenclature......Page 22
Adiabatic Calorimetry......Page 23
Calorimeter Selection for Pharmaceutical Studies......Page 24
OPERATING PRINCIPLES......Page 25
Heat Conduction Calorimetry......Page 26
Tian Equation......Page 29
Dynamic Data Correction......Page 31
Determination of Time Constants......Page 35
Electrical Calibration......Page 37
Chemical Test Reactions......Page 39
Flow Calorimetry......Page 40
Solution Calorimetry......Page 41
Flow Calorimetry......Page 42
Titration Calorimetry......Page 43
Gas Perfusion Calorimetry......Page 44
Solution Calorimetry......Page 46
Semi-Adiabatic Solution Calorimeters......Page 48
Differential Scanning Calorimetry......Page 50
Information from Differential Scanning Calorimetry Data......Page 51
Fast-Scan Differential Scanning Calorimetry......Page 54
High-Sensitivity Differential Scanning Calorimetry......Page 55
Temperature-Modulated Differential Scanning Calorimetry......Page 56
SUMMARY......Page 57
Journals......Page 58
REFERENCES......Page 59
INTRODUCTION......Page 63
Location of the Instrument......Page 64
Glass Ampoules......Page 65
Choice of Reference......Page 66
CALIBRATION AND VALIDATION......Page 67
Electrical Calibration......Page 68
Limitations of Electrical Calibration......Page 69
Chemical Test Reactions......Page 70
Chemical Test Reactions......Page 71
GOOD PRACTICE FOR TITRATION CALORIMETRY......Page 73
Chemical Test Reactions......Page 75
Data Interpretation......Page 76
GOOD PRACTICE FOR SOLUTION CALORIMETRY......Page 77
Chemical Test Reactions......Page 78
GOOD PRACTICE FOR PERFUSION CALORIMETRY......Page 80
Calibration......Page 81
GOOD PRACTICE FOR FLOW CALORIMETRY......Page 82
Chemical Test Reactions......Page 83
APPLICATIONS OF TEST AND REFERENCE REACTIONS......Page 84
Incorrect Assignment of a Baseline......Page 85
Incorrect Assignment of an Upper Power Limit......Page 86
Nonuniform Error......Page 88
Time-Dependent Error......Page 89
Nonlinear Drift......Page 91
Error Caused by the Thermostat......Page 92
Effect of Fill Volume......Page 93
SPECIAL CONSIDERATIONS FOR FLOW CALORIMETERS......Page 96
Determination of Thermal Volume......Page 97
Flow Calorimetric Equations......Page 98
Secondary Test Reactions for Flow Calorimeters......Page 99
Experimental Arrangement......Page 101
Effect of Flow Rate on Residence Time......Page 102
SUMMARY......Page 108
REFERENCES......Page 109
INTRODUCTION......Page 113
EMPIRICAL FITTING......Page 114
KINETIC MODELING......Page 115
A Practical Example......Page 116
Parallel First- and Second-Order Reactions with the Same Reactant......Page 120
Parallel First- and Higher-Order Reactions with Different Reactants......Page 123
Simulation of Consecutive Reactions......Page 128
Consecutive, First-Order, … Reactions......Page 130
Consecutive, First-Order, … Reactions......Page 131
Consecutive First-Order … Reactions......Page 135
First-Order, Parallel-Consecutive…Reactions......Page 142
Concurrent Reaction Schemes......Page 148
Flow Calorimetry......Page 149
Flow-Mix Calorimeters......Page 154
Flow-Through Calorimeters......Page 156
CALCULATION VS. ITERATION......Page 158
CALCULATION TECHNIQUES......Page 159
Calculation for the Initial Calorimetric Signal Phi0......Page 160
Calculation for the Reaction Order......Page 161
Calculation for the Total Heat Released for Complete Reaction......Page 164
Calculation for Reaction Half-Life......Page 165
Calculation for a Rate Constant from Flow Calorimetric Data......Page 166
Test for Complete Reaction......Page 167
Calculation of QT......Page 168
Extension to More Complex Reaction Schemes......Page 170
Theoretical Development......Page 171
Determination of Q......Page 172
Limitations of the Method......Page 173
Chemometric Analysis......Page 175
Principles of Chemometrics......Page 176
Application to Calorimetric Data......Page 178
Calculation of Reaction Enthalpies for Complex Data Sets......Page 179
Determination of DeltaH from Two Heat–Time Data......Page 180
REFERENCES......Page 182
INTRODUCTION......Page 185
USE OF DIFFERENTIAL SCANNING CALORIMETRY IN PREFORMULATION......Page 186
Purity Determination......Page 187
Theory......Page 188
Determination of Polymorphs......Page 191
Measurement of Polymorphic Composition......Page 193
Stability/Compatibility......Page 195
Determination of Solubility for Ideal Solutions......Page 197
Determination of Solubility for Nonideal Solutions......Page 198
Limitations for the Measurement of Solubility......Page 199
Glass Transition Temperature......Page 201
Purity Determination......Page 202
Determination of Polymorphs......Page 203
Determination of Solubility......Page 204
Determination of Enthalpy of Solution by Solution Calorimetry......Page 206
Determination of the Enthalpy of Solution Using Step-Isothermal Methods......Page 207
Enthalpy of Solution by Flow Calorimetry......Page 208
Stability/Compatibility......Page 210
Prediction of Compatibility......Page 211
Limitations of the Step-Isothermal Technique......Page 212
Packaging Material......Page 213
Dissolution Characteristics of a Formulation......Page 214
Assessment of Dissolution Characteristics by Isothermal Calorimetry......Page 215
Hygroscopicity......Page 216
SUMMARY......Page 217
REFERENCES......Page 218
INTRODUCTION......Page 224
APPLICATION OF ISOTHERMAL TITRATION CALORIMETRY TO RATIONAL DRUG DESIGN......Page 225
Experimental Design......Page 227
Measurement of the Binding Stoichiometry......Page 228
Measurement of the Binding Affinity......Page 229
Binding Thermodynamics......Page 233
Practical Considerations......Page 234
Applications in Drug Development......Page 236
LEAD OPTIMIZATION USING ISOTHERMAL FLOW CALORIMETRY......Page 238
Calorimetry for Following Microbial Growth......Page 240
Ampoule Calorimeters......Page 241
Flow Calorimeters......Page 242
Form of Calorimetric Output......Page 243
Calorimetric Analysis of Drugs......Page 244
SUMMARY......Page 251
REFERENCES......Page 252
INTRODUCTION......Page 256
Theory of Formation......Page 257
Effects of Amorphous Materials......Page 260
AGING OF AMORPHOUS MATERIAL......Page 262
Potential Impact of Small Amorphous Contents......Page 266
Calorimetric Methods......Page 269
Preparation of Calibration Curves......Page 283
Isothermal Calorimetry......Page 284
Solution Calorimetry......Page 289
SUMMARY......Page 291
REFERENCES......Page 292
INTRODUCTION......Page 295
CURRENT METHODS FOR STABILITY ASSESSMENT......Page 296
Primary Screening......Page 301
Stability Assessment of Individual Compounds......Page 307
Hydrolysis Reactions......Page 308
Oxidation......Page 322
Elevated Relative Humidity Studies......Page 324
Photostability......Page 326
Stability Assessment of Active Pharmaceutical Ingredient–Excipient Mixtures......Page 329
Stability Assessment of Formulated Products......Page 331
REFERENCES......Page 335
WHOLE SYSTEM MEASUREMENTS......Page 341
Measurement of Enthalpies of Transfer......Page 342
Measurement of the Swelling of Polymers, Compacts, and Hydrogels......Page 343
Measurement of Drug Dissolution......Page 349
Assessment of Photostability......Page 350
APPLICATIONS TO PROCESS SCALE-UP AND PROCESS ANALYTICAL TECHNOLOGY......Page 352
Process Monitoring......Page 353
Integrated Circuit Calorimeters......Page 354
SUMMARY......Page 356
REFERENCES......Page 357