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Crystallization of Organic Compounds, 2nd Edition
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Crystallization of Organic Compounds, 2nd Edition
by Hsien-Hsin Tung, Edward L. Paul, Michael Midler, James A. McCauley
Crystallization of Organic Compounds, 2nd Edition
Cover
Title Page
Copyright Page
Preface
Chapter 1: Introduction to Crystallization
Chapter 2: Properties
Chapter 3: Polymorphism
Chapter 4: Kinetics
Chapter 5: Mixing and Crystallization
Chapter 6: Critical Issues and Quality by Design
Chapter 7: Cooling Crystallization
Chapter 8: Evaporative Crystallization
Chapter 9: Anti‐solvent Crystallization
Chapter 10: Reactive Crystallization
Chapter 11: Filtration
Chapter 12: Drying
Chapter 13: Special Applications
References
Index
End User License Agreement
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Title Page
Table of Contents
Cover
Title Page
Copyright Page
Preface
Chapter 1: Introduction to Crystallization
1.1 CRYSTAL PROPERTIES AND POLYMORPHS (CHAPTERS 2 AND 3)
1.2 NUCLEATION AND GROWTH KINETICS (CHAPTER 4)
1.3 MIXING AND SCALE‐UP (CHAPTER 5)
1.4 CRITICAL ISSUES AND QUALITY BY DESIGN (CHAPTER 6)
1.5 CRYSTALLIZATION PROCESS OPTIONS (CHAPTERS 7–10)
1.6 DOWNSTREAM OPERATIONS (CHAPTERS 11 AND 12)
1.7 SPECIAL APPLICATIONS (CHAPTER 13)
Chapter 2: Properties
2.1 SOLUBILITY
2.2 SUPERSATURATION, METASTABLE ZONE, AND INDUCTION TIME
2.3 OIL, AMORPHOUS, AND CRYSTALLINE STATES
2.4 POLYMORPHISM
2.5 SOLVATE
2.6 SOLID COMPOUND, SOLID SOLUTION, AND SOLID MIXTURE
2.7 INCLUSION AND OCCLUSION
2.8 ADSORPTION, HYGROSCOPICITY, AND DELIQUESCE
2.9 CRYSTAL MORPHOLOGY
2.10 PARTICAL SIZE DISTRIBUTION AND SURFACE AREA
Chapter 3: Polymorphism
3.1 PHASE RULE
3.2 PHASE TRANSITION
3.3 PREDICTION OF CRYSTAL STRUCTURE AND ITS FORMATION
3.4 SELECTION AND SCREENING OF CRYSTAL FORMS
3.5 EXAMPLES
Chapter 4: Kinetics
4.1 SUPERSATURATION AND RATE PROCESSES
4.2 NUCLEATION
4.3 CRYSTAL GROWTH AND AGGLOMERATION
4.4 NUCLEATE/SEED AGING AND OSTWALD RIPENING
4.5 DELIVERED PRODUCT: PURITY, CYSTAL FORM, SIZE AND MORPHOLOGY, AND CHEMICAL AND PHYSICAL STABILITY
4.6 DESIGN OF EXPERIMENT (DOE)—MODEL‐BASED APPROACH
4.7 MODEL‐FREE FEEDBACK CONTROL
Chapter 5: Mixing and Crystallization
5.1 INTRODUCTION
5.2 MIXING CONSIDERATIONS AND FACTORS
5.3 MIXING EFFECTS ON NUCLEATION
5.4 MIXING EFFECTS ON CRYSTAL GROWTH
5.5 MIXING DISTRIBUTION AND SCALE‐UP
5.6 CRYSTALLIZATION EQUIPMENT
5.7 PROCESS DESIGN AND EXAMPLES
Chapter 6: Critical Issues and Quality by Design
6.1 QUALITY BY DESIGN
6.2 BASIC PROPERTIES
6.3 SEED
6.4 SUPERSATURATION
6.5 MIXING AND SCALE—SELECTION OF EQUIPMENT AND OPERATING PROCEDURES
6.6 STRATEGIC CONSIDERATIONS FOR CRYSTALLIZATION PROCESS DEVELOPMENT
6.7 SUMMARY OF CRITICAL ISSUES
Chapter 7: Cooling Crystallization
7.1 BATCH OPERATION
7.2 CONTINUOUS OPERATIONS
7.3 PROCESS DESIGN—EXAMPLES
Chapter 8: Evaporative Crystallization
8.1 INTRODUCTION
8.2 SOLUBILITY DIAGRAMS
8.3 FACTORS AFFECTING NUCLEATION AND GROWTH
8.4 SCALE‐UP
8.5 EQUIPMENT
8.6 PROCESS DESIGN AND EXAMPLES
Chapter 9: Anti‐solvent Crystallization
9.1 OPERATION
9.2 IN‐LINE MIXING CRYSTALLIZATION
9.3 PROCESS DESIGN AND EXAMPLES
Chapter 10: Reactive Crystallization
10.1 INTRODUCTION
10.2 CONTROL OF PARTICLE SIZE
10.3 KEY ISSUES IN ORGANIC REACTIVE CRYSTALLIZATION
10.4 CREATION OF FINE PARTICLES—IN‐LINE REACTIVE CRYSTALLIZATION
10.5 PROCESS DESIGN AND SCALE‐UP
Chapter 11: Filtration
11.1 INTRODUCTION
11.2 BASIC PROPERTIES
11.3 KINETICS
11.4 PROCESS DESIGN AND SCALE‐UP
Chapter 12: Drying
12.1 INTRODUCTION
12.2 BASIC PROPERTIES
12.3 KINETICS
12.4 PROCESS DESIGN AND SCALE‐UP
Chapter 13: Special Applications
13.1 INTRODUCTION
13.2 CRYSTALLIZATION WITH SUPERCRITICAL FLUIDS
13.3 RESOLUTION OF STEREO‐ISOMERS
13.4 WET MILLS IN CRYSTALLIZATION
13.5 COMPUTATIONAL FLUID DYNAMICS IN CRYSTALLIZATION
13.6 SOLID DISPERSION—CRYSTALLINE AND/OR AMORPHOUS DRUGS
13.7 PROCESS DESIGN AND EXAMPLES
References
Index
End User License Agreement
List of Tables
Chapter 3
Table 3.1 Difference of lattice energy and solubility among polymorphs and ...
Table 3.2 A partial list of acid counterion candidates for salt screening....
Table 3.3 A partial list of base counterion candidates for salt screening....
Table 3.4 A partial list of amino acid counterion candidates for salt scree...
Table 3.5 A partial list of coformer candidates for co‐crystal screening.
Table 3.6 Solubility (mg/ml) of Indomethacin Forms I, II, and III in aqueou...
Table 3.7 Solubility of sulindac Forms I and II in ethyl acetate.
Table 3.8 Dissolution of sulindac Forms I and II in 29.3%
n
‐propanol‐water....
Table 3.9 Hygroscopicity study with HCl salt of Example 3.6 at room tempera...
Table 3.10 Solubility study in water with HCl salt of Example 3.6.
Chapter 4
Table 4.1 First‐order growth rate constants (fluidized bed versus CSTR crys...
Table 4.2 Crystal form conversion time with and without high shear.
Table 4.3 Effect of extent of seed or initial nucleation on final crystal p...
Table 4.4 Nucleation and crystal growth rate in different solvent systems....
Chapter 5
Table 5.1 Mixing in crystallizers for pharmaceutical processes.
Table 5.2 Mixing intensity landscape of different methods.
Table 5.3 Glass‐lined impellers and their methods of attachment.
Table 5.4 Recommended minimum
V
f
/V
t
for selected geometries for turbulent f...
Table 5.5 Particle size data among different commercial sites.
Table 5.6 Comparison of mixing indexes among factories.
Chapter 6
Table 6.1 Characteristics of generation of supersaturation.
Chapter 7
Table 7.1 Experimental conditions and results of crystallization.
Table 7.2 Solubility of the R
/
S‐Ibuprofen‐S‐Lysine in ethanol
/
water 97
/
3 so...
Table 7.3 Results of resolution of Ibuprofen lysinate.
Table 7.4 Experimental conditions and results of polymorphs.
Table 7.5 First‐order growth rate constants (fluidized bed versus CSTR crys...
Table 7.6 Rate constants for crystal breakage
(slurry concentration).
Chapter 8
Table 8.1 Comparison of process options.
Chapter 9
Table 9.1 Conditions and results of slurry and crystallization experiments....
Table 9.2 Modification of antisolvent addition.
Table 9.3 Input and output variable for design of experiments.
Table 9.4 Impact of solvent ratio, temperature, and concentration on produc...
Table 9.5 “DFP” plasma level.
Chapter 10
Table 10.1 Impact of experimental conditions on residual solvent in the cak...
Table 10.2 Comparison of performance between original and modified process....
Chapter 11
Table 11.1 Types of material used as filter medium.
Table 11.2 Filtration cake resistance ranking.
Table 11.3 Residual t‐BuOH and DMSO in the final API cake.
Table 11.4 Design of slurry/wash composition.
Table 11.5 Residual t‐BuOH and DMSO in the cake.
Chapter 12
Table 12.1 Brittleness index versus size reduction after hammer milling....
Table 12.2 Assessment of particle fracture and agglomeration tendency.
Table 12.3 Drying profile and particle behaviors during drying.
Table 12.4 Characteristics of different dryer.
Table 12.5 Residual acetone level in the laboratory investigation.
Chapter 13
Table 13.1 Experimental results of the original process versus the two‐filt...
Table 13.2 Freeze crystallization cycles (all acetone levels).
Table 13.3 Imipenem crystallinity and phase behavior of acetone
/
water.
Table 13.4 API crystallinity in ASD and hybrid solid dispersion.
List of Illustrations
Chapter 2
Figure 2.1 Free energy‐composition phase diagram.
Figure 2.2 Solubility of lovastatin in different solvent mixtures as a funct...
Figure 2.3 Solubility of lovastatin as a function of solvent composition.
Figure 2.4 Atypical solubility behavior reaching a maximum at a certain solv...
Figure 2.5 Impact of impurities on solubility.
Figure 2.6 Impact of chemical structure on the solubility of lovastatin (com...
Figure 2.7 NRTL‐SAC prediction of solubility for Lovastatin Simvastatin, Eto...
Figure 2.8 Comparison of predicted and measured Lovastatin solubility—predic...
Figure 2.9 Experimental glass transition temperature (
T
g
) profiles (left plo...
Figure 2.10 Solubility and metastable zone width.
Figure 2.11 Free energy‐composition phase diagram for metastable zone region...
Figure 2.12 Solution concentration profile during crystallization.
Figure 2.13 Expanded map on metastable zone width.
Figure 2.14 Formation of oil droplets of a highly supersaturated solution.
Figure 2.15 Formation of amorphous solid after aging of oil droplets.
Figure 2.16 Formation of crystalline solid.
Figure 2.17 (a) Solubility, miscibility, and
T
g
curves of solid dispersion. ...
Figure 2.18 Solubility curves of monotropic and enantiotropic polymorphs.
Figure 2.19 Solubility of form I and III polymorphs of a reverse transcripta...
Figure 2.20 Conversion of forms I and III mixture to form I after aging.
Figure 2.21 Solubility diagram of solvate and non‐solvate at different tempe...
Figure 2.22 Solubility of anhydrous solid and monohydrate of ibuprofen lysin...
Figure 2.23 Anhydrate versus monohydrate crystals of ibuprofen‐lysinate.
Figure 2.24 Phase diagram for the case of solid compound.
Figure 2.25 Phase diagram for the case of solid solution.
Figure 2.26 Solubilities of chemically similar APIs: lovastatin and simvasta...
Figure 2.27 Crystal cavity and crystal aggregates.
Figure 2.28 Adsorption of R‐ibu‐S‐Lys on S‐Ibu‐S‐lys.
Figure 2.29 Vapor–solid adsorption isotherm.
Figure 2.30 Residual ethanol level in the wet cake during drying.
Figure 2.31 Needle‐like, plate‐like, and cube‐like crystals.
Figure 2.32 Heat/cool/wet mill cycles for improvement of crystal aspect rati...
Figure 2.33 Particle size distribution functions,
Q
(
x
),
dQ
(
x
), and
q
(
x
).
Chapter 3
Figure 3.1 Crystal unit cell diagram, caffeine as model compound.
Figure 3.2 Caffeine molecule orientation in unit cell (looking down the
C
‐ax...
Figure 3.3 (a) and (b) Crystal energy landscape for isocaffeine (a) and caff...
Figure 3.4 Free energy profile as a function of nucleus/cluster size.
Figure 3.5 Energy barrier of
α
and
β
crystals
Figure 3.6 Nucleation rate of
α
and
β
crystals.
Figure 3.7 Hydrogen bonding network in crystal structure of co‐crystals.
Figure 3.8 Degradation pathway of Ritonavir—the ester bond is hydrolized, an...
Figure 3.9 DTA for indomethacin Forms I and II (left) and I and III (right)....
Figure 3.10 DTA for sulindac Forms I and II.
Figure 3.11 Solubility and dissolution for sulindac.
Figure 3.12 DSC thermograms for losartan before (curve A) and after (curve B...
Figure 3.13 Solubility data for losartan.
Figure 3.14 XRPD patterns of Forms I and II of Proscar (Finasteride).
Figure 3.15 DSC profiles of Forms I and II of Proscar (Finasteride).
Figure 3.16 DSC profiles of ibuprofen lysinate.
Figure 3.17 Cyclic DSC for ibuprofen lysinate (heat/cool cycle).
Figure 3.18 The XRPD patterns (left) and the TG curves (right) of forms Type...
Figure 3.19 Additional XRPD patterns of anhydrous forms.
Figure 3.20 XRPD patterns for compound A, Forms I and II.
Figure 3.21 Solid‐state NMR for compound A, (a) Forms I and (b) Form II (*re...
Figure 3.22 DSC thermogram for compound A, Forms I and II.
Figure 3.23 XRPD patterns for compound A, Forms III and IV.
Figure 3.24 Solid‐state NMR for compound A, (a) Forms III and (b) Form IV.
Figure 3.25 Solubility data for compound A, Forms I and II in
t
‐butyl acetat...
Figure 3.26 XRPD patterns for prednisolone
t‐
butylacetate.
Figure 3.27 Experimental and calculated XRPD patterns of Form I hydrate (lef...
Figure 3.28
Block A
is hydrate;
Block B
shows water presence on crystal surf...
Figure 3.29 DTA and
T
g
curve for phthalusulfaithiazole.
Figure 3.30 Thermal decomposition pathway for phthalusulfaithiazole.
Chapter 4
Figure 4.1 Effect of supersaturation on growth rate and particle size.
Figure 4.2 Mechanisms of nucleation.
Figure 4.3 Contributions to Gibbs free energy for homogeneous embryo formati...
Figure 4.4 Effect of supersaturation on free energy of cluster formation.
Figure 4.5 Stress on surface molecules in a cluster or crystal can alter its...
Figure 4.6 A schematic representation of the solution depletion in the vicin...
Figure 4.7 Nucleation on a foreign particle for different wetting angles.
Figure 4.8 Measurement of nucleation kinetics for barium sulfate.
Figure 4.9 Measurement of nucleation kinetics and induction time for lovasta...
Figure 4.10 Effect of supersaturation on growth characteristics of MgSO
4
·7H
2
Figure 4.11 A schematic representation of dendrite coarsening.
Figure 4.12 Effect of agitator speed on the secondary nucleation rate for st...
Figure 4.13 Surface structure of a growing crystal: (a) one attachment, (b) ...
Figure 4.14 Formation of a two‐dimensional critical nucleus on a crystal sur...
Figure 4.15 A screw dislocation in a simple cubic crystal. AB, BC are disloc...
Figure 4.16 Development of a growth spiral starting from a screw dislocation...
Figure 4.17 Examples of spiral crystal growth.
Figure 4.18 Distinct adsorption sites for additives and impurities: (a) kink...
Figure 4.19 Low levels of impurity can affect crystal morphology: three view...
Figure 4.20 Shown is 2.5‐order growth for a pharmaceutical compound solubili...
Figure 4.21 Mechanism of aggregation/agglomeration.
Figure 4.22 Crystallization with (left) and without (right) agglomeration.
Figure 4.23 Fluidized bed crystallizer growth rate test apparatus.
Figure 4.24 Size and number intervals for computation of population density....
Figure 4.25 Graphic representation of the population balance of the MSMPR cr...
Figure 4.26 Summary of semi‐logarithmic population density plots and potenti...
Figure 4.27 Methods of seed generation and corresponding size ranges.
Figure 4.28 Generic diagram showing a crystallizer with an external recircul...
Figure 4.29 Typical crystal shapes.
Figure 4.30 Cooling profiles and mass ratio of three experiments.
Figure 4.31 In silico screening of seed impact on crystallization.
Figure 4.32 Microscopic photos of crystals under different supersaturation—2...
Chapter 5
Figure 5.1 Relationship between mixing time and scale.
Figure 5.2 Relationship between agitator rpm and crystallizer volume, under ...
Figure 5.3 Impact of mixing intensity on de‐agglomeration: agglomerates with...
Figure 5.4 Impact of mixing intensity on particle breakage/attrition.
Figure 5.5 Reaction yield as a function of the reaction Da number; mixing se...
Figure 5.6 Particle size as a function of a crystallization Da number (the r...
Figure 5.7 Schematic representation of concentration gradients from bulk sol...
Figure 5.8 Impact of mixing intensity on crystal growth.
Figure 5.9 Comparison of mixing uniformity (using micro‐mixing time) of diff...
Figure 5.10 Comparison of mixing uniformity (using micro‐mixing time) of dif...
Figure 5.11 Typical stirred vessel crystallizer.
Figure 5.12 GlasLock
®
glass‐lined steel impellers.
Figure 5.13 Cryo‐Lock
®
impellers.
Figure 5.14 ElcoLock
®
and fixed impellers
®
impellers.
Figure 5.15 Configuration of a single stage rotor/stator mixer—top view (lef...
Figure 5.16 Fluidized bed crystallizer and dissolver.
Figure 5.17 Impinging jet crystallizer.
Figure 5.18 Mean particle size data as a function of tip speed with varying ...
Figure 5.19 Vessel fill‐up volume among factories.
Chapter 6
Figure 6.1 Four types of supersaturation generation.
Figure 6.2 Effect of time of addition of an anti‐solvent or reagent on super...
Figure 6.3 Effect of supersaturation on nucleation, growth, and nucleate par...
Figure 6.4 Comparison of the growth rate of hexamethylene tetramine crystals...
Chapter 7
Figure 7.1 Solution concentration time profile.
Figure 7.2 Nucleation versus supersaturation.
Figure 7.3 Natural cooling versus linear and controlled cooling.
Figure 7.4 Effect of impurities on conversion of crystal forms.
Figure 7.5 Typical flow pattern for a continuous crystallizer.
Figure 7.6 Feedforward
/
feedback crystallizer control.
Figure 7.7 (a–c) Flow patterns in mixed suspension crystallizers.
Figure 7.8 Simplified information flow for an MSMPR crystallizer.
Figure 7.9 Cascade operation.
Figure 7.10 Flow in an Oslo cooling crystallizer.
Figure 7.11 Product from seeding and cooling process (200×).
Figure 7.12 Steep temperature‐solubility slope for a desired intermediate.
Figure 7.13 Flow in a mixing elbow.
Figure 7.14 Product crystals (200×).
Figure 7.15 Profiles of total particle counts.
Figure 7.16 Profiles of mean particle size.
Figure 7.17 Profile of total particle counts during cool‐down.
Figure 7.18 Profile of mean particle size (area‐based) during cool‐down.
Figure 7.19 Particle size distribution of lab and factory materials at the e...
Figure 7.20 Final particle size using 1 and 5 wt% seed.
Figure 7.21 Final particle size before and after sonication.
Figure 7.22 Resolution of ibuprofen with S‐lysine.
Figure 7.23 Solubility phase diagram.
Figure 7.24 Flowsheet of preferential crystallization.
Figure 7.25 Flowsheet of crystallization with control crystal form.
Figure 7.26 Typical flow pattern for continuous stirred tank separation of s...
Figure 7.27 Typical flow pattern for fluidized bed separation of stereoisome...
Figure 7.28 Unsonicated crystals (left); sonicated (right).
Figure 7.29 Crystals entering (left) and leaving (right) a flow sonication u...
Figure 7.30 Factory fluidized bed crystallizers.
Chapter 8
Figure 8.1 Concentration profiles for crystallization by evaporation as a fu...
Figure 8.2 Concentration profiles for crystallization by evaporation when th...
Figure 8.3 Concentration profiles for crystallization by evaporation when th...
Figure 8.4 A standard jacketed stirred tank with baffles and an overhead con...
Figure 8.5 A standard jacketed stirred tank for evaporative crystallization ...
Figure 8.6 A concentration profile for uncontrolled crystallization by evapo...
Figure 8.7 A concentration profile for a controlled crystallization by evapo...
Figure 8.8 Crystals of batch‐mode crystallization (a) as a slurry and (b) as...
Figure 8.9 Crystals of semi‐continuous crystallization (a) as a slurry and (...
Figure 8.10 Microscopic photo of crystals (left: ethanolate, right: hydrate)...
Figure 8.11 Distillation mode—forward addition (left) and reverse addition (...
Figure 8.12 Sticky gums on the crystallizer wall and phase inversion mechani...
Chapter 9
Figure 9.1 Concentration profiles for normal addition of anti‐solvent to bat...
Figure 9.2 Concentration profile for reverse addition (solute solution to an...
Figure 9.3 Addition rate profile for linear (curve A) and programmed (curve ...
Figure 9.4 Solubility and supersaturation profiles for the linear and optimu...
Figure 9.5 Profile of factory material crystallized with a CBT at low impell...
Figure 9.6 Profile of a lab run crystallized with a PBT, using an appropriat...
Figure 9.7 Typical crystalline product in Example 9.1 before changes in mixi...
Figure 9.8 Typical crystalline product in Example 9.1 after changes in impel...
Figure 9.9 Molecular structures of RRR and SSR isomers.
Figure 9.10 Solubility of RRR and SSR at 20°C in aqueous ethanol in pure sol...
Figure 9.11 Supernatant concentration of RRR and SSR isomers at different so...
Figure 9.12 Scanning electron microscopic photographs of crystals for Exampl...
Figure 9.13 Flow sheet of the antisolvent addition procedure Option 1.
Figure 9.14 Antisolvent addition procedure for Option 2.
Figure 9.15 Effect of crystal size on filtration rate for Option 3. The data...
Figure 9.16 Effect of percentage of fines on filtration rate for Option 3. T...
Figure 9.17 Microscopic photo of crystals for Option 1 (left, normal additio...
Figure 9.18 Microscopic photo of crystals for Example 9.4, Option 4 (DMF/IPA...
Figure 9.19 PSD of crystals for Example 9.4, Option 4 (forward vs reverse ad...
Figure 9.20 A common flow diagram for impinging jet crystallization.
Figure 9.21 Impinging jet crystallization has very high volumetric productiv...
Figure 9.22 Impinging jet crystallization—surface area versus supersaturatio...
Figure 9.23 (a) Photomicrographs of equal surface area products obtained by ...
Figure 9.24 Chemical structure of DFP, an API candidate utilizing impinging ...
Figure 9.25 Schematic of the impinging jet crystallizer showing the option t...
Figure 9.26 Microscopic photos of (a) direct jet and (b) recycle jet crystal...
Figure 9.27 Surface area as a function of supersaturation. The higher the su...
Figure 9.28 PSD of the same compound (DFP) crystallized by impinging jet com...
Figure 9.29 Process flow diagram of in situ wet seed and particle generation...
Figure 9.30 PLM images of crystals generated by the in situ wet seed/particl...
Figure 9.31 Agglomerated particles with wide variation of particle size dist...
Figure 9.32 Nonagglomerated particles with uniform and robust particle size ...
Chapter 10
Figure 10.1 Schematic representation of addition modes for reagents in react...
Figure 10.2 Schematic representation of reagent addition time (overall time ...
Figure 10.3 Impinging jet crystallization apparatus.
Figure 10.4 Size distribution of calcium oxalate crystallized at (a) 2 and (...
Figure 10.5 Photographs of impingement planes in a free jet (a) at feed velo...
Figure 10.6 Size distribution of sodium cefuroxime crystallized by conventio...
Figure 10.7 (a) Needles from the reactive crystallization (b) Crystals after...
Figure 10.8 (a) Crystals showing a bimodal distribution during crystallizati...
Figure 10.9 (a) Bimodal distribution from the original process showing fines...
Figure 10.10 Reagent addition time effect on the supersaturation experienced...
Figure 10.11 Flowchart for the simultaneous addition of stream A containing ...
Figure 10.12 Microscopic photo of crystals. Some layering of crystals is app...
Figure 10.13 Residual solvent in the cake as a function of the ratio of time...
Figure 10.14 Simultaneous addition with wet milled heel seed.
Figure 10.15 Crystals from the original process and the revised process afte...
Chapter 11
Figure 11.1 Classification of filtration operations.
Figure 11.2 Filtration and washing steps—Step 1: solid–liquid separation, St...
Figure 11.3 Driving force in filtration/washing.(
Note
:
P
1
>
P
2
for pot‐typ...
Figure 11.4 Filtration resistance—cake and medium.
Figure 11.5 Filtrate concentration profiles (curves
a
,
b
,
c
) during filtrati...
Figure 11.6 Cake wash with channeling and mother liquor left‐over.
Figure 11.7 Effect of wet cake saturation level on washing efficiency.
Figure 11.8 Particle image and size distribution before and after the washin...
Figure 11.9 Filtrate impurity profile after each wash.
Figure 11.10 Impurity concentration in the filtrate after each wash.
Figure 11.11 Filtration profile of
t
/
V
over
V
, under different
∆P
.
Figure 11.12 Filtration rate vs. slurry settling rate.
Figure 11.13 (a) Filtration operation—agitated filter. (b) Filtration operat...
Chapter 12
Figure 12.1 V–L equilibrium of acetone, water, and heptane.
Figure 12.2 Water vapor pressure and water activity.
Figure 12.3 Hydration behavior of different hydrates under different humidit...
Figure 12.4 Stress–strain relationship.
Figure 12.5 Relationship between granule wetness and granule size/torque. Op...
Figure 12.6 Relationship between formation of large agglomerates, torque val...
Figure 12.7 (a) Torque and wetness relationship of three different particle ...
Figure 12.8 Drying profiles: induction, constant rate, and falling rate stag...
Figure 12.9 Drying profiles with different nitrogen sweep modes.
Figure 12.10 Impact of mixing energy and cake wetness on fracturing, agglome...
Figure 12.11 Dryers with different mixing/blending patterns.
Figure 12.12 Residual solvents versus wet cake weight (top) and wet cake LOD...
Figure 12.13 Starting material.
Figure 12.14 Comparison of particle agglomeration/fracturing behavior of rot...
Chapter 13
Figure 13.1 Solubility curve in aqueous solution showing the width of the me...
Figure 13.2 Flowsheet for Example 13.1; feed preparation and crystallization...
Figure 13.3 (a) The very large cubic crystals have grown in aqueous solution...
Figure 13.4 Photomicrographs of antibiotic crystals; the sharpness of the cr...
Figure 13.5 Concentration profiles for a consecutive–competitive reaction sh...
Figure 13.6 Effect of the solubility of the desired product,
R
, in the react...
Figure 13.7 Effect of the addition time of reagent
B
on the yield
/
selectivit...
Figure 13.8 Chemical reaction of Example 13.3.
Figure 13.9 Flowsheet of the original process of Example 13.3.
Figure 13.10 Solubility of Mono and Iso in the toluene mother liquor of Exam...
Figure 13.11 Flowsheet of the two‐filtration process with recycle of second ...
Figure 13.12 (a) DMSO and active carbon absorption isotherms at room tempera...
Figure 13.13 Chemical structure of imipenem.
Figure 13.14 DSC thermograms for 10, 20, and 30% acetone
/
water solutions.
Figure 13.17 DSC thermograms for 30% acetone
/
water and imipenem
/
NaHCO
3
in a ...
Figure 13.18 Relationship between the degree of crystallinity of imipenem an...
Figure 13.19 Flowsheet of stereoisomer resolution systems.
Figure 13.20 (a) Fluidization behavior of particular solids in a (liquid) fl...
Figure 13.21 (a) The histogram plots the actual column data versus the ideal...
Figure 13.22 (a) Sonicators located at the bottom of the column. (b) Fines g...
Figure 13.23 The sonicator is an external circulation loop.
Figure 13.24 The calculations for the particles in a fluidized bed.
Figure 13.25 (a) Different relative scales of some actual fluidized bed crys...
Figure 13.26 Comparison of dissolution profile of hybrid solid dispersion an...
Figure 13.27 Microscope images of ASD samples before and after dispersed in ...
Figure 13.28 Microscopic Images of hybrid samples before and after dispersed...
Figure 13.29 DSC profiles of physical mixture, ASD and hybrid solid dispersi...
Guide
Cover Page
Title Page
Copyright Page
Preface
Table of Contents
Begin Reading
References
Index
WILEY END USER LICENSE AGREEMENT
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