CR 8: Recommended Procedures
     Number 1 Introduction
         Number 1.0 Introduction to Recommended Procedures
             1. INTRODUCTION
             2. CONTEXT
             3. SCOPE AND STRUCTURE
             4. SAFETY CONSIDERATIONS
             5. APPLICABILITY
             6. REPORTING PROBLEMS AND SUGGESTED IMPROVEMENTS
             7. REVISIONS
             8. APPENDIX 1 FEED BACK FORM
         Number 1.1 Research Strategy
         Number 1.2 Library Searches
             Number 1.2.1 Organic Crystallization
                 1. INTRODUCTION
                 2. CONTEXT
                 3. SEARCHING STRATEGY
                 4. STRUCTURE
                 5. DEFINING THE SYSTEM
                 6. INFORMATION REQUIRED
                 7. SOURCES OF INFORMATION
                 8. STORAGE AND HANDLING OF INFORMATION
                 9. APPENDIX 1 EXAMPLE OF A COMPLETED SEARCH SPECIFICATION
                 10. APPENDIX 2 EXAMPLE OF A RECORD OF A SEARCH OF THE GENERAL LITERATURE
                 11. APPENDIX 3 EXAMPLE OF WISNIAK / WISNIAK AND HERSKOWITZ SEARCH
                 12. APPENDIX 4 EXAMPLE OF STAGE 1 OF A MANUAL CHEMICAL ABSTRACTS SEARCH
                 13. APPENDIX 5 EXAMPLE OF STAGE 2 OF A MANUAL CHEMICAL ABSTRACTS SEARCH
             Number 1.2.2 Inorganic Crystallization
                 1. INTRODUCTION
                 2. CONTEXT
                 3. SEARCHING STRATEGY
                 4. STRUCTURE
                 5. DEFINING THE SYSTEM
                 6. INFORMATION REQUIRED
                 7. SOURCES OF INFORMATION
                 8. STORAGE AND HANDLING OF INFORMATION
                 9. APPENDIX 1 EXAMPLE OF A COMPLETED SEARCH SPECIFICATION
                 10. APPENDIX 2 EXAMPLE OF A SEARCH OF THE GENERAL LITERATURE
                 11. APPENDIX 3 EXAMPLE OF A COMPLETED RECORD OF WISNIAK / WISNIAK AND HERSKOWITZ SEARCH
                 12. APPENDIX 4 STAGE 1 OF A MANUAL CHEMICAL ABSTRACTS SEARCH
                 13. APPENDIX 5 STAGE 2 OF A MANUAL CHEMICAL ABSTRACTS SEARCH
         Number 1.3 Laboratory Procedures
             Number 1.3.1 Record Keeping and Labelling
             Number 1.3.2 Presentation of Data
         Number 1.5 Sample handing
             Number 1.5.1 Retention of Samples
             Number 1.5.2 Disposal of Waste Material
     Number 2 Solution Characterisation
         Number 2.1 Composition
             Number 2.1.1 Analysis by HPLC
             Number 2.1.2 Analysis by GC
             Number 2.1.3 Analysis by IR Spectroscopy
             Number 2.1.4 Analysis by UV Spectroscopy
             Number 2.1.5 Analysis by Atomic Absorption
         Number 2.2 Concentration
             Number 2.2.1 Evaporation to Dryness
                 1. INTRODUCTION
                 2. CONTEXT
                 3. STRUCTURE
                 4. SAFETY CONSIDERATIONS
                 5. LIMITATIONS OF THE TECHNIQUE
                 6. PRELIMINARY WORK PRIOR TO SAMPLING
                 7. POST SAMPLING PROCEDURE
                 8. DATA HANDLING
                 9. POSSIBLE PROBLEMS
                 10. REFERENCES
             Number 2.2.2 Refractometry
             Number 2.2.3 Densitometry
                 1. INTRODUCTION
                 2. CONTEXT
                 3. LIMITATIONS
                 4. STRUCTURE OF RECOMMENDED PROCEDURE
                 5. RELATED SPS RECOMMENDED PROCEDURES
                 6. RELATED SPS REPORTS
                 7. PROCEDURE
         Number 2.3 Solubility
             Number 2.3.1 General Comments
                 1. INTRODUCTION
                 2. CONTEXT
                 3. STRUCTURE
                 4. RELATED RECOMMENDED PROCEDURES
                 5. POTENTIAL PROBLEMS TO BE AWARE OF
                 6. THE DESIGN OF AND CONDUCT OF EXPERIMENTS
             Number 2.3.2 Experimental Strategy
                 1. INTRODUCTION
                 2. CONTEXT
                 3. STRUCTURE
                 4. RELATED RECOMMENDED PROCEDURES
                 5. PREPARATION OF AN EXPERIMENTAL STRATEGY
                 6. APPENDIX 1 AN EXAMPLE OF A COMPLETED EXPERIMENTAL STRATEGY
                 7. APPENDIX 2 AN EXAMPLE OF A BLANK EXPERIMENTAL STRATEGY
             Number 2.3.3 Experimental Apparatus
                 1. INTRODUCTION
                 2. CONTEXT
                 3. STRUCTURE
                 4. RELATED RECOMMENDED PROCEDURES
                 5. SAFETY CONSIDERATIONS
                 6. EXPERIMENTAL EQUIPMENT
             Number 2.3.4 Preparing and Sampling a Saturated Solution
                 1. INTRODUCTION
                 2. CONTEXT
                 3. STRUCTURE
                 4. PRELIMINARY CHECKS
                 5. EQUILIBRATION FROM UNDER-SATURATION
                 6. EQUILIBRATION FROM OVER-SATURATION
                 7. SAMPLING PROCEDURE
                 8. TERMINATING THE EXPERIMENT
                 9. REUSING THE SLURRY FOR A FURTHER EXPERIMENT
                 10. IN THE EVENT OF A TEMPERATURE EXCURSION
                 11. RESULTS HANDLING PROCEDURES
                 12. APPENDIX 1 AN EXAMPLE OF A COMPLETED SET OF EXPERIMENTAL REPORT FORMS
                 13. APPENDIX 2 EXPERIMENTAL REPORT FORMS: EQUILIBRATION RATE AND SOLUBILITY
         Number 2.4 Supersaturation
         Number 2.5 Density
         Number 2.6 Viscosity
         Number 2.7 Thermodynamic Properties by Solution Calorimetry
     Number 3 Solid Phase Characterisation
         Number 3.1 Sampling
         Number 3.2 Direct Observation
             Number 3.2.1 Optical Microscopy
                 1. INTRODUCTION
                 2. CONTEXT
                 3. STRUCTURE
                 4. RELATED RECOMMENDED PROCEDURES
                 5. SAFETY CONSIDERATIONS
                 6. PRELIMINARY CHECKS
                 7. INITIAL VISUAL INSPECTION
                 8. LOW MAGNIFICATION - HAND LENS
                 9. INTERMEDIATE MAGNIFICATION - STEREO MICROSCOPE
                 10. INTERMEDIATE AND HIGH MAGNIFICATION - RESEARCH MICROSCOPE
                 11. APPENDIX 1 EXAMPLE OF A COMPLETED MICROSCOPIC EXAMINATION REPORT
                 12. APPENDIX 2 RECORD OF MICROSCOPIC EXAMINATION
             Number 3.2.2 Electron Microscopy
         Number 3.3 Size
             Number 3.3.1 Sieving
                 1. INTRODUCTION
                 2. CONTEXT
                 3. STRUCTURE
                 4. RELATED RECOMMENDED PROCEDURES
                 5. SAFETY CONSIDERATIONS
                 6. PRELIMINARY CHECKS
                 7. SAMPLE PREPARATION
                 8. SIEVING PROCEDURE
                 9. SAMPLE RETENTION
                 10. DATA PRESENTATION
                 11. DEALING WITH DIFFICULT TO SIEVE MATERIALS
                 12. APPENDIX 1 EXAMPLE OF A COMPLETED TEST SIEVING REPORT FORM
                 13. APPENDIX 2 TEST SIEVING REPORT FORM
             Number 3.3.2 Malvern 2600
             Number 3.3.3 Coulter Counter
             Number 3.3.4 WASP
         Number 3.4 Shape
             Number 3.4.1 Shape Factors for Sieving
                 1. INTRODUCTION
                 2. CONTEXT
                 3. STRUCTURE
                 4. RELATED RECOMMENDED PROCEDURES
                 5. PRELIMINARY CHECKS
                 6. SAMPLE PREPARATION
                 7. BASIC COUNTING AND WEIGHING PROCEDURE
                 8. ADVANCED COUNTING AND WEIGHING PROCEDURE
                 9. DATA PRESENTATION
                 10. APPENDIX 1 EXAMPLE OF SIEVE CALIBRATION BY COUNTING AN WEIGHING
                 11. APPENDIX 2 RECORD OF SIEVE CALIBRATION BY COUNTING AND WEIGHING
             Number 3.4.2 Crystal Habit and Perfection
         Number 3.5 Size Distribution
         Number 3.6 Filterability
             Number 3.6.1 Filtration Testing Procedure
                 1. INTRODUCTION
                 2. CONTEXT
                 3. STRUCTURE
                 4. SAFETY CONSIDERATIONS
                 5. SETTING UP
                 6. PREPARATION OF A CRYSTAL SLURRY
                 7. FILTRATION TEST
                 8. ANALYSIS AND INTERPRETATION OF RESULTS
                 9. POSSIBLE PROBLEMS
                 10. REFERENCES
                 11. APPENDIX 1 EXAMPLE OF THE EXPERIMENTAL REPORT FORM
                 12. APPENDIX 2 EXAMPLE OF THE EXPERIMENTAL REPORT FORM
         Number 3.7 Phase
             Number 3.7.1 DSC Analysis of Crystal Shapes
             Number 3.7.2 TGA of Crystal Shapes
         Number 3.8 Purity
     Number 4 Equipment
         Number 4.1 Crystallizer Hydrodynamics
             Number 4.1.1 Determination of Flow Patterns
                 1. INTRODUCTION
                 2. CONTEXT
                 3. STRUCTURE
                 4. RELATED RECOMMENDED PROCEDURES
                 5. EXPERIMENTAL EQUIPMENT
                 6. EXPERIMENTAL PROCEDURE
                 7. FLOW PATTERN PRESENTATION
             Number 4.1.2 Determination of Mixing Rates
                 1. INTRODUCTION
                 2. CONTEXT
                 3. STRUCTURE
                 4. RELATED SPS RECOMMENDED PROCEDURES
                 5. RELATED SPS RESEARCH REPORTS
                 6. EXPERIMENTAL EQUIPMENT
                 7. EXPERIMENTAL PROCEDURE
                 8. PRESENTATION OF MIXING TIME DATA
             Number 4.1.3 Determination of Turnover Time
                 1. INTRODUCTION
                 2. CONTEXT
                 3. STRUCTURE
                 4. RELATED SPS RECOMMENDED PROCEDURES
                 5. RELATED SPS RESEARCH REPORTS
                 6. EXPERIMENTAL EQUIPMENT
                 7. EXPERIMENTAL PROCEDURE
                 8. DATA PRESENTATION
             Number 4.1.4 Determination of Solids Distribution
                 1. INTRODUCTION
                 2. CONTEXT
                 3. STRUCTURE
                 4. RELATED SPS RECOMMENDED PROCEDURES
                 5. RELATED SPS RESEARCH REPORTS
                 6. EXPERIMENTAL EQUIPMENT
                 7. EXPERIMENTAL PROCEDURE
                 8. DATA PRESENTATION
         Number 4.2 Mixing
         Number 4.3 Heat and Mass Transfer
     Number 5 Miscellaneous Experimental
         Number 5.1 Growth of Large Crystals
     Number 6 Growth and Nucleation
         Number 6.0 Scoping Experiments for Measuring Crystallization Kinetics
             1. INTRODUCTION
             2. CONTEXT
             3. STRUCTURE
             4. PRELIMINARY CHECKS AND EQUIPMENT PREPARATION
             5. SOLUTION PREPARATION
             6. METASTABLE ZONE WIDTH AND DESUPERSATURATION RATE
             7. SAMPLING PROCEDURE
             8. RECOVERING THE PRODUCT CRYSTALS
             9. CHARACTERISING THE PRODUCT CRYSTALS
             10. PLOTTING THE DESUPERSATURATION RATE
             11. RESULTS INTERPRETATION AND METHOD SELECTION
             12. APPENDIX 1 EXPERIMENTAL REPORT FORMS:
             13. APPENDIX 2 AN EXAMPLE OF A COMPLETED SET OF EXPERIMENTAL REPORT FORMS
         Number 6.1 Metastable Zone Width
             Number 6.1.1 Determination of Metastable Zone Width
                 1. INTRODUCTION
                 2. CONTEXT
                 3. STRUCTURE
                 4. APPARATUS
                 5. PREPARATION OF A SATURATED SOLUTION
                 6. RAPID GENERATION OF SUPERSATURATION
                 7. CONTROLLED GENERATION OF SUPERSATURATION
                 8. ANALYSIS AND INTERPRETATION OF RESULTS
                 9. POSSIBLE PROBLEMS
                 10. APPENDIX 1 EXAMPLE EXPERIMENTAL REPORT FORM
                 11. APPENDIX 2 EXPERIMENTAL REPORT FORM
         Number 6.2 Batch Experimental Techniques
             Number 6.2.1 Controlled Crystallization Tests
                 1. INTRODUCTION
                 2. CONTEXT
                 3. STRUCTURE
                 4. PRELIMINARY CHECKS AND SETTING UP
                 5. SOLUTION PREPARATION
                 6. EXPERIMENTAL PROCEDURE
                 7. SOLUTION SAMPLING PROCEDURE
                 8. SLURRY SAMPLING PROCEDURE
                 9. TERMINATING THE EXPERIMENT
                 10. REUSING THE SLURRY FOR A FURTHER EXPERIMENT
                 11. RESULTS HANDLING PROCEDURES
                 12. APPENDIX 1 EXPERIMENTAL REPORT FORMS:
                 13. APPENDIX 2 AN EXAMPLE OF A COMPLETED SET OF EXPERIMENTAL REPORT FORMS
         Number 6.3 Continuous Experimental Techniques
             Number 6.3.1 Determination of Crystallization Kinetics in a MSMPR Continuous Crystallizer using a Population Balance Technique
                 1. INTRODUCTION
                 2. CONTEXT
                 3. STRUCTURE OF RECOMMENDED PROCEDURE
                 4. RELATED SPS RECOMMENDED PROCEDURES
                 5. RELATED SPS REPORTS
                 6. EXPERIMENTAL PROCEDURE
                 7. ANALYTICAL PROCEDURE
         Number 6.4 Growth Kinetics
             Number 6.4.1 Determination of Crystal Growth Rate
         Number 6.5 Dissolution Kinetics
         Number 6.6 Nucleation Kinetics
     Number 7 Miscellaneous
         Number 7.1 Chiral Crystallization
             1. INTRODUCTION
             2. SCOPE AND CONTEXT
             3. STRUCTURE
             4. CHARACTERISATION OF THE CRYSTALLINE RACEMATE
             5. PROCEDURE FOR RESOLVING CONGLOMERATES
             6. RESOLUTION USING A CHIRAL AUXILIARY

Volume VIII contains step-by-step procedures for carrying out specific tasks associated with crystallization work. These procedures encapsulate our own practical knowledge, and will be regularly updated as procedures are developed or improved.

Procedures currently available:

 

 

A number of further procedures are available in draft form, contact the Crystallization Manager for details.