1. What is crystallization?
Crystallization is a solid–liquid separation process where a solute forms pure solid crystals from a solution.
Driven by supersaturation, which is the key driving force.
Used for purification, particle size control, and product recovery.
Produces high-purity solids compared to other separation methods.
2. Types of crystallizers used in industry.
Batch Cooling Crystallizer – simple, used for pharma & fine chemicals.
Forced Circulation Crystallizer – for large scale, handles high viscosity.
Draft Tube Baffle (DTB) Crystallizer – excellent for large uniform crystals.
MSMPR Crystallizer – continuous type for steady product quality.
Vacuum Cooling Crystallizer – used when solute is heat-sensitive.
Melt Crystallizer – for very high purity separation.
3. Difference between cooling crystallization and evaporative crystallization.
Cooling Crystallization
Supersaturation created by reducing temperature.
Used for temperature-dependent solubility systems.
Cooling rate controls crystal size.
Evaporative Crystallization
Supersaturation created by removing solvent (evaporation).
Used when solubility is less temperature-dependent.
Works well with vacuum to reduce boiling point.
4. What is supersaturation?
Supersaturation = condition where solution contains more solute than its equilibrium solubility.
It is the driving force for nucleation and crystal growth.
Formula:
Supersaturation (S) = C – C*
Where,
C = actual concentration
C* = saturation concentration
5. Methods to achieve supersaturation.
Cooling – decreases solubility.
Evaporation – removes solvent.
Anti-solvent addition – reduces solubility quickly.
Chemical reaction – forms a less soluble product.
pH shift crystallization – shifts solubility based on acidic/basic species.
6. Define nucleation and its types.
Nucleation is the initial formation of small stable crystals from a supersaturated solution.
It decides crystal number and size distribution.
Types:
Primary Nucleation – occurs without existing crystals.
Homogeneous
Heterogeneous
Secondary Nucleation – induced by existing crystals due to collision or agitation.
7. What is crystal growth?
Process where solute molecules deposit layer-by-layer on an existing crystal.
Determines final crystal size, shape, and quality.
Growth rate depends on supersaturation, temperature, agitation, and impurities.
General Growth Rate Formula:
G = k · (S − 1)^g
Where,
G = crystal growth rate
k = rate constant
S = supersaturation ratio
g = growth exponent
8. Factors affecting nucleation and crystal growth.
Supersaturation level – higher S → more nucleation; lower S → more growth.
Cooling rate – fast cooling → fines; slow cooling → large crystals.
Agitation speed – affects secondary nucleation.
Impurities – may inhibit growth or change crystal habit.
Solvent type – affects solute solubility and crystal arrangement.
Seeding quality – influences uniform PSD.
9. Importance of solubility curve in crystallization.
Helps identify saturation, metastable, and unstable regions.
Guides selection of cooling profile.
Helps maintain solution within metastable zone to avoid uncontrolled nucleation.
Allows prediction of yield and crystal size.
Essential for designing batch and continuous crystallizers.
10. What is metastable zone width (MZW)?
MZW = temperature or concentration range where solution is supersaturated but stable (no spontaneous nucleation).
Determines how much supersaturation can be applied without unwanted fines.
Wider MZW → more flexibility in controlling crystal size.
Narrow MZW → requires precise control of cooling and seeding.
Formula:
MZW = T_nucleation − T_saturation
11. How do you control crystal size distribution (CSD)?
Maintain supersaturation within the metastable zone.
Use proper seeding (quantity, size, timing).
Apply controlled cooling rate to avoid excessive fines.
Optimize agitation speed to balance mixing without breakage.
Use classification zones (DTB/OSLO) for larger uniform crystals.
Minimize impurities that alter growth.
12. Role of agitation in crystallization.
Ensures uniform mixing and even supersaturation.
Helps maintain temperature uniformity.
Promotes secondary nucleation (to a limited extent).
Prevents settling and localized supersaturation.
Excessive agitation causes crystal breakage and fines → poor PSD.
13. What is crystal seeding? Why is it done?
Seeding = addition of pre-formed crystals to a supersaturated solution.
Controls nucleation point, promoting controlled crystal growth.
Ensures consistent particle size distribution.
Reduces risk of uncontrolled spontaneous nucleation.
Improves batch-to-batch uniformity and product quality.
14. Types of seeding methods.
Dry Seeding – addition of dry crystals.
Slurry Seeding – seed crystals dispersed in solvent.
Programmed Seeding – controlled addition based on supersaturation.
Continuous Seeding (in continuous crystallizers).
Attrition/Agglomeration Seeding – fine crystals formed by shear.
15. What is an MSMPR crystallizer?
MSMPR = Mixed Suspension Mixed Product Removal crystallizer.
A continuous crystallizer with uniform suspension and continuous output.
Used to study population balance and steady-state PSD.
Simple design; widely used for kinetic studies and large volumes.
16. Working principle of Forced Circulation Crystallizer.
Solution is pumped through a circulation loop and heated to near saturation.
Slurry flows through heat exchanger, evaporates partially → supersaturation.
Crystals grow in the main body, not inside tubes → avoids fouling.
Suitable for high viscosity and salts; ensures larger crystal formation.
17. Working principle of Draft Tube Baffle (DTB) Crystallizer.
Has a draft tube, propeller, and baffle arrangement.
Creates controlled circulation for separation of fines and growth of coarse crystals.
Fines move upward and dissolve; large crystals move downward and exit.
Produces high-purity, large-sized, uniform crystals.
Ideal for continuous operation and products requiring narrow PSD.
18. Difference between batch and continuous crystallizers.
Batch Crystallizers
Time-based, flexible, used for pharma and specialty chemicals.
Suitable for small batches and product variety.
Easier control of cooling profile and seeding.
Continuous Crystallizers
Steady-state operation; used for large-scale production.
Consistent PSD and quality.
Higher efficiency and throughput.
19. What is magma density?
Magma density = ratio of mass of crystals to mass of mother liquor.
Indicates solids loading inside the crystallizer.
High magma density → higher productivity but may affect mixing and circulation.
Low magma density → lower yield and slow growth.
Formula:
Magma Density = (Mass of Crystals) / (Mass of Mother Liquor)
20. How do impurities affect crystallization?
Reduce crystal growth rate by blocking active sites.
Cause habit modification (irregular or needle-like crystals).
Increase nucleation, producing excess fines.
Reduce purity due to entrapment.
May lead to oiling out or secondary phases.
Affect filtration and drying performance.
21. What is yield in crystallization?
Yield represents the amount of solute recovered as crystals from the total solute available.
Indicates process efficiency.
Affected by solubility, cooling profile, impurities, and filtration losses.
Formula:
Yield (%) = (Mass of Crystals / Mass of Solute in Feed) × 100
22. Common operational problems in crystallizers.
Fouling / scaling on heat transfer surfaces.
Excessive fines formation due to high supersaturation.
Crystal breakage from high agitation.
Low yield because of poor cooling rate or improper seeding.
Blockage in discharge line due to high slurry density.
Agglomeration leading to poor filtration.
23. What is crystal habit?
Crystal habit = external shape or morphology of a crystal.
Influences flowability, filtration, drying, and downstream handling.
Controlled by supersaturation, impurities, solvent, and additives.
24. How to control crystal habit?
Adjust supersaturation to promote uniform growth.
Use habit modifiers (additives) to change specific crystal faces.
Select suitable solvent or anti-solvent.
Optimize temperature profile to avoid rapid nucleation.
Control impurities, as they can distort the habit.
25. What is mother liquor?
Mother liquor is the remaining liquid after crystals are separated.
Contains uncrystallized solute, impurities, and solvent.
Often recycled to improve recovery.
Quality of mother liquor directly affects crystal purity and yield.
26. Why filtration becomes difficult in crystallization?
Fines formation → slow filtration and clogging.
Highly viscous mother liquor → poor drainage.
Irregular or needle-shaped crystals → create dense cake.
Agglomeration reduces permeability.
Entrapped impurities increase stickiness.
27. Heat transfer requirements in crystallizers.
Maintain uniform temperature gradient to control supersaturation.
Require high heat transfer area to avoid local hot spots.
Use jacketed vessels, heat exchangers, or calandrias.
Design must prevent fouling and scaling.
Smooth heat removal → consistent crystal growth.
28. Role of vacuum in crystallization.
Lowers boiling point → suitable for heat-sensitive materials.
Enhances evaporative crystallization at lower temperatures.
Helps maintain supersaturation without thermal degradation.
Improves energy efficiency in large-scale systems.
29. What is anti-solvent crystallization?
Process where a second solvent (anti-solvent) is added to reduce solubility of solute.
Rapid supersaturation → nucleation.
Used for heat-sensitive, high-purity, or poorly soluble materials.
Critical to control addition rate to avoid excess fines.
Ensures narrow particle size distribution when done properly.
30. Difference between primary and secondary nucleation.
Primary Nucleation
Occurs without existing crystals.
Driven purely by supersaturation.
Common during initial stages of crystallization.
Secondary Nucleation
Occurs in presence of existing crystals.
Caused by collisions, attrition, or fluid shear.
Dominant in industrial crystallizers due to agitation.
31. What is polymorphism in crystals?
Polymorphism = ability of a compound to exist in more than one crystal structure.
Different polymorphs have different solubility, stability, melting point, and bioavailability.
Critical in pharmaceutical industry for product quality and regulatory compliance.
Controlled by solvent, temperature, supersaturation, and cooling rate.
32. Importance of cooling rate in crystal formation.
Slow cooling → low supersaturation → fewer nuclei → larger, uniform crystals.
Fast cooling → high supersaturation → many nuclei → fine crystals.
Affects CSD, filtration, yield, and crystal habit.
Cooling profile must stay within metastable zone for best results.
33. What is Ostwald ripening?
Phenomenon where small crystals dissolve and material deposits on larger crystals.
Occurs due to difference in solubility of small vs large crystals.
Leads to wider PSD and loss of fines.
Controlled by supersaturation, temperature, and agitation.
34. Scaling and fouling issues in crystallizers.
Caused by supersaturated fluid depositing on walls or heat transfer tubes.
Reduces heat transfer efficiency.
Leads to flow restriction, pressure drop, and poor crystal quality.
Controlled by:
Maintaining correct supersaturation
Proper circulation velocity
Use of anti-foulants
Periodic cleaning (CIP)
35. Differences between crystallization and precipitation.
Crystallization
Controlled cooling/evaporation.
Slow growth → well-defined crystals.
High purity.
Precipitation
Rapid mixing or reaction.
Immediate nucleation → fine particles.
Lower purity, more amorphous solids.
36. How to measure crystal size (analytical tools)?
Laser Diffraction (PSD Analyzer)
Microscopy (optical, SEM)
Focused Beam Reflectance Measurement (FBRM)
Sieving (for coarse crystals)
Image analysis software
Tools provide real-time or offline crystal size distribution.
37. What is slurry density?
Slurry density = amount of solids per unit volume of slurry.
Affects viscosity, pumping, and filtration.
High slurry density → risk of blockage and poor circulation.
Controlled by crystal loading, cooling rate, and residence time.
Formula:
Slurry Density = (Mass of Solids) / (Total Volume of Slurry)
38. Material balance in crystallizer.
Material balance ensures mass input = mass output + accumulation.
Used to calculate crystal yield, solvent loss, recycle requirement.
Helps design flow rates, seeding amount, and mother liquor recycle.
General Formula:
Input = Output + Accumulation
39. Energy balance in crystallizer.
Ensures correct heat removal or addition for crystal formation.
Key for controlling cooling load, evaporation rate, and supersaturation.
Includes heating/cooling duties, latent heat, and mixing effects.
Improper energy balance leads to uncontrolled nucleation.
General Formula:
Q = m · Cp · ΔT
Q = heat duty
m = mass flow rate
Cp = heat capacity
ΔT = temperature change
40. What parameters are monitored during crystallizer operation?
Temperature profile
Supersaturation level
Agitation speed
Slurry density / Magma density
Particle size distribution (PSD)
pH (if applicable)
Flow rates (feed, mother liquor recycle)
Vacuum level (for evaporative systems)
Conductivity / Turbidity for real-time monitoring
41. Crystallizer start-up procedure.
Charge solvent and solute to required level.
Start agitation and ensure uniform mixing.
Heat or cool to reach near-saturation condition.
Establish circulation flow (for DTB/Forced Circulation).
Create controlled supersaturation using cooling/evaporation.
Add seeds (if required).
Stabilize parameters: temperature, flow, vacuum, supersaturation.
Begin steady-state operation for continuous units.
42. Crystallizer shutdown procedure.
Stop feed and allow system to reach equilibrium.
Remove remaining slurry/crystals from vessel.
Flush system with solvent to remove deposits.
Gradually stop agitation and circulation pumps.
Clean heat exchanger surfaces to avoid scaling.
Vent vessel and secure valves for safe shutdown.
43. Safety hazards in crystallizer operation.
Overpressure due to blocked lines or vapor generation.
Vacuum hazards (implosion risk).
Chemical exposure from solvent vapors and hot liquids.
Mechanical hazards from rotating agitators.
Thermal hazards from hot surfaces.
Slip hazards from spills during discharge.
Controlled via PPE, interlocks, alarms, and proper housekeeping.
44. What is encrustation and how to prevent it?
Encrustation = deposition of crystals or solids on heat transfer surfaces.
Reduces heat transfer efficiency and increases fouling.
Preventive actions:
Maintain minimal supersaturation in heat exchanger tubes.
High circulation velocity to avoid stagnant zones.
Use smooth surfaces and anti-foul coatings.
Regular CIP/chemical cleaning.
Correct cooling rate to avoid local crystallization.
45. Common troubleshooting steps for crystallizers.
If fines increase → reduce cooling rate, check seeding.
If large crystals not forming → adjust supersaturation or growth time.
If scaling → increase circulation velocity or clean HX.
If low yield → optimize solubility curve, mother liquor recycle.
If blockage → reduce slurry density or increase agitation.
Use PAT tools (FBRM, PVM) for real-time diagnosis.
46. What is population balance in crystallization?
Mathematical model describing number and size distribution of crystals in a crystallizer.
Considers nucleation, growth, agglomeration, breakage.
Used to design MSMPR and understand PSD behavior.
Helps control steady-state crystallizer operations.
47. Explain crystal agglomeration.
Agglomeration = joining of small crystals to form a larger cluster.
Occurs due to high supersaturation, poor mixing, sticky surfaces.
Leads to poor filterability and broad PSD.
Controlled by:
Optimizing cooling rate
Using anti-agglomeration additives
Ensuring proper agitation
48. What is breakage and attrition of crystals?
Breakage: physical fracture into pieces due to shear or collisions.
Attrition: slow wearing away of edges during mixing.
Caused by high agitation, pump shear, or high slurry density.
Leads to excess fines and reduced product quality.
Controlled by adjusting impeller speed and crystal residence time.
49. How is supersaturation measured in practice?
Indirect methods:
Using solubility curve and temperature sensor.
Density or refractive index measurement.
Direct PAT tools:
ATR–FTIR for concentration monitoring.
Conductivity probes (for salts).
FBRM to track nucleation and growth.
Supersaturation = key control parameter for CSD.
50. What is the role of solvents in crystallization?
Solvent determines solubility profile and supersaturation behavior.
Affects polymorph formation and crystal habit.
Impacts yield, purity, and filtration properties.
Must be chosen based on selectivity, boiling point, viscosity, and compatibility.
Solvent mixture can optimize anti-solvent crystallization.
51. Explain vacuum cooling crystallization.
Vacuum reduces the boiling point of the solvent.
When pressure is lowered suddenly, part of the solvent flash-evaporates, causing rapid cooling.
Cooling → supersaturation → crystallization.
Suitable for heat-sensitive products and temperature-sensitive solubility systems.
Offers fast cooling and reduced thermal degradation risk.
52. What is flash crystallization?
Hot saturated solution enters a low-pressure chamber.
Instant solvent evaporation (“flash”) → sudden cooling.
Generates high supersaturation → rapid nucleation.
Used when quick crystallization is required.
Needs careful control to avoid overproduction of fines.
53. Why is controlled cooling important?
Prevents uncontrolled nucleation and excess fines.
Maintains solution within metastable zone width (MZW).
Ensures uniform crystal growth → better PSD.
Reduces risk of scaling, agglomeration, and poor filtration.
Key for batch crystallizer consistency.
54. What is the impact of viscosity on crystallization?
High viscosity → slow mass transfer, slower crystal growth.
Poor mixing → localized supersaturation → fines formation.
Increases agglomeration and hampers slurry circulation.
Affects filtration and drying due to mother liquor retention.
Controlled through temperature, solvent selection, and dilution.
55. Explain solute recovery in crystallization.
Solute recovery = percentage of solute retrieved as crystals.
Improved by:
Optimized cooling/evaporation profile
Mother liquor recycle
Reducing impurities that increase solubility
Proper seeding to enhance growth
High recovery → reduced solvent usage and cost.
Formula:
Solute Recovery (%) = (Recovered Solute / Initial Solute) × 100
56. Why do we use baffles in crystallizers?
Prevent vortex formation during agitation.
Improve bulk mixing and uniform supersaturation.
Enhance heat transfer and prevent settling.
Reduce dead zones → uniform crystal growth.
Essential for achieving consistent PSD.
57. What is the role of draft tube in DTB crystallizer?
Ensures controlled circulation of slurry from bottom to top.
Creates a defined flow pattern for fines dissolution and coarse crystal growth.
Separates growth zone and classification zone.
Helps achieve large, uniform crystals.
Reduces wall fouling and improves overall efficiency.
58. Explain the principle of melt crystallization.
Involves solidifying a melt (pure liquid of solute) without solvent.
Impurities remain in the liquid phase; pure solid crystals form.
Used for high-purity separations (e.g., organic chemicals).
Eliminates solvent handling and reduces environmental impact.
Includes methods like sweating, layer crystallization, and suspension crystallization.
59. What is purge stream in crystallizer?
A small side-stream removed to prevent accumulation of impurities in mother liquor.
Maintains steady-state purity in continuous crystallizers.
Avoids impurity buildup that affects crystal habit and growth.
Purged stream is often sent to recovery or waste treatment.
60. How to reduce fines generation?
Maintain supersaturation within MZW.
Use slow, controlled cooling.
Optimize seed quantity and size.
Reduce agitation intensity to avoid attrition.
Implement classification (DTB/OSLO) to dissolve fines.
Minimize impurities, as they promote nucleation.
61. What is crystal slurry?
Crystal slurry = mixture of solid crystals suspended in mother liquor.
Represents the working mass inside crystallizers.
Its properties (density, viscosity, PSD) affect mixing, pumping, filtration, and discharge.
Controlled by cooling rate, seeding, and circulation flow.
62. Why is residence time important?
Determines how long crystals stay inside the crystallizer.
Longer residence time → larger crystals & narrow PSD.
Short residence time → more fines & lower yield.
Crucial in continuous crystallizers for maintaining steady-state PSD.
Formula:
Residence Time = (Volume of Crystallizer) / (Flow Rate)
63. What is a growth curve in crystallization?
A plot showing crystal size vs time.
Indicates how fast crystals grow under given conditions.
Helps determine optimal supersaturation and cooling rate.
Used for modeling crystal kinetics and scale-up.
Essential for improving batch reproducibility.
64. Explain the purpose of a classifier (elutriation leg).
Separates fines from coarse crystals based on settling velocity.
Fines move upward and dissolve; coarse crystals move downward for removal.
Ensures uniform particle size and high product purity.
Key part of DTB and OSLO crystallizers.
65. What is MSMPR (Mixed Suspension Mixed Product Removal)?
A continuous crystallizer where suspension is perfectly mixed and product is continuously withdrawn.
Produces steady-state crystal size distribution.
Used for population balance modeling and process scale-up.
Ideal for large-scale salt and bulk chemical crystallization.
66. Define suspension density.
Suspension density = amount of solids present per unit volume in a crystal slurry.
Affects pumpability, mixing, and heat transfer.
High suspension density → risk of blockage and poor circulation.
Must be optimized for efficient crystallization and filtration.
67. Why is crystallizer holdup important?
Holdup = amount of material present inside system (liquid + crystals).
Determines residence time, yield, and PSD.
High holdup → better growth time but higher energy use.
Low holdup → insufficient growth → fines formation.
Critical for continuous crystallizer design.
68. Explain equilibrium solubility.
Solubility = maximum amount of solute that can dissolve in solvent at given temperature.
Determines saturation concentration (C*).
Affects supersaturation, yield, and cooling curve.
Solubility curve helps plan cooling profile and seeding strategy.
Basic relation:
Supersaturation (S) = C – C*
C = actual concentration
C* = equilibrium solubility
69. What is cooling profile?
Controlled temperature reduction during crystallization.
Designed to remain within metastable zone width (MZW).
Influences nucleation rate, growth, PSD, and yield.
Smooth cooling → large crystals
Aggressive cooling → fines formation
70. Effect of agitation speed on crystal size.
Low agitation → poor mixing → uneven supersaturation → agglomeration.
Optimal agitation → uniform mixing, controlled nucleation, consistent PSD.
High agitation → crystal breakage, attrition, excessive fines.
Agitation must balance mass transfer and mechanical stress.
71. Why do we use controlled addition in anti-solvent crystallization?
Avoids instantaneous nucleation and fines formation.
Maintains supersaturation within metastable zone.
Ensures uniform crystal growth instead of rapid precipitation.
Prevents localized concentration gradients.
Improves PSD, purity, and filtration performance.
72. What are common scale inhibitors?
Chemicals added to prevent deposition on heat-transfer surfaces.
Typical inhibitors include:
Polyphosphates
Polyacrylates
EDTA / chelating agents
Organophosphonates
Work by blocking crystal nucleation sites or modifying crystal growth.
Reduce fouling, cleaning frequency, and downtime.
73. What is heterogeneous nucleation?
Nucleation occurring on foreign surfaces or impurities.
Requires lower supersaturation compared to homogeneous nucleation.
Common sources: vessel walls, dust particles, seed crystals.
Often desirable (controlled seeding) but can also cause fouling.
74. Purpose of mother liquor recycle.
Improves overall yield by recovering dissolved solute.
Reduces solvent consumption.
Maintains steady-state concentration and impurity levels.
Stabilizes feed composition in continuous crystallizers.
Helps in achieving consistent crystal quality.
75. Explain fines removal in DTB crystallizer.
Fines migrate to upper classification zone.
They dissolve due to higher temperature / lower supersaturation.
Coarse crystals settle and grow in the growth zone.
Improves PSD uniformity, enhances product purity.
Ensures large, well-defined crystals.
76. Why do we monitor turbidity during crystallization?
Turbidity increases when nucleation starts.
Acts as an indirect indicator of particle concentration.
Helps identify onset of crystallization, controlling seeding time.
Useful for end-point detection in batch crystallization.
Part of PAT for maintaining consistent PSD.
77. What is batch-to-batch consistency issue?
Variation in PSD, yield, or purity between batches.
Caused by changes in:
Cooling rate
Seeding quality
Supersaturation level
Impurities in feed
Controlled by standardizing recipe, PAT sensors, and tight parameter control.
78. What is crystal loading?
Also called solids loading = percentage of crystals in slurry.
Affects viscosity, pumping, heat transfer, and CSD.
High loading → poor circulation, blockage.
Low loading → insufficient growth.
Needs optimization for stable operation and filterability.
79. How to avoid crystal breakage?
Maintain optimal agitation speed (avoid high shear).
Use gentle circulation pumps (low shear impellers).
Reduce slurry density to avoid collisions.
Avoid rapid temperature changes that cause stress.
Control supersaturation to prevent brittle crystal formation.
80. Explain the concept of crystal purity.
Purity refers to absence of impurities trapped inside or on the crystal surface.
Depends on:
Growth rate (slower growth → higher purity)
Impurity level in mother liquor
Washing efficiency
Crystal habit and morphology
High purity desired for pharma-grade materials.
81. What is boiling point elevation?
Increase in boiling point due to dissolved solutes in the solvent.
Affects evaporative crystallizer performance.
Higher boiling point → more energy required for evaporation.
Must be considered in heat balance and vacuum design.
82. Why vacuum is used in evaporative crystallizer?
Reduces boiling point → lower temperature evaporation.
Protects heat-sensitive materials from degradation.
Enhances evaporation rate without increasing temperature.
Improves energy efficiency and operational safety.
83. What is the impact of high impurity load?
Alters crystal habit and morphology.
Promotes excess nucleation → fines formation.
Increases mother liquor viscosity → poor circulation.
Reduces product purity due to entrapment.
May cause oiling out or secondary phase formation.
84. Explain crystallizer heat load calculation.
Heat load = amount of heat that must be removed or supplied to achieve crystallization.
Includes sensible heat, latent heat of evaporation, and heat of crystallization.
Formula:
Q = m × Cp × ΔT
Where:
Q = heat duty
m = mass flow
Cp = heat capacity
ΔT = temperature change
Essential for sizing heat exchangers, jackets, and chillers.
85. What is slurry pump recirculation ratio?
Ratio of circulation flow through pump to crystallizer feed flow.
Higher ratio → better mixing, uniform supersaturation.
Low ratio → localized supersaturation → scaling/fines.
Typical industrial recirculation ratio: 5:1 to 20:1 depending on design.
86. Why is particle size distribution (PSD) important?
Determines filterability, flowability, and downstream efficiency.
Affects product quality, especially in pharma APIs.
Impacts drying time, final purity, and tablet compression.
Controlled by cooling rate, supersaturation, seeding, and agitation.
87. How do you prevent crystal fouling on heat transfer surfaces?
Maintain high circulation velocity to prevent stagnant zones.
Keep supersaturation low inside heat exchanger tubes.
Use polished surfaces or anti-fouling coatings.
Implement CIP routines and periodic descaling.
Control temperature gradient to avoid local crystallization.
88. What is crystallizer capacity?
Maximum amount of crystal mass a crystallizer can process efficiently.
Depends on:
Working volume
Heat transfer capacity
Circulation rate
Mother liquor saturation
Solids loading limit
Overloading leads to poor mixing, scaling, and blockage.
89. Why are centrifuges used after crystallization?
To separate crystals from mother liquor.
Provide faster, more efficient separation than filtration.
Reduce moisture content for better drying performance.
Suitable for handling wide PSD ranges and high slurry densities.
Improve overall product purity through wash cycles.
90. What are common energy-saving methods in crystallizers?
Use multiple-effect evaporators.
Apply vacuum to reduce heating requirement.
Implement heat recovery systems (condensate reuse).
Optimize cooling profile to minimize refrigeration load.
Improve insulation to prevent heat loss.
Maintain clean heat-transfer surfaces to maximize efficiency.
91. Explain nucleation kinetics.
Describes rate of new crystal formation as a function of supersaturation.
Depends on temperature, impurities, agitation, and solvent.
Higher supersaturation → higher nucleation rate.
Important for controlling PSD, fines formation, and consistency.
General form:
B = k · (S − 1)^b
B = nucleation rate
k = rate constant
S = supersaturation ratio
b = nucleation exponent
92. What is supersaturation ratio?
Dimensionless measure of how much solute exceeds its solubility.
Indicates available driving force for nucleation and growth.
Formula:
S = C / C*
C = actual concentration
C* = saturation concentration
S > 1 → supersaturated (crystallization possible)
S = 1 → saturated
S < 1 → undersaturated
93. What is the effect of solvent selection?
Determines solubility and supersaturation behavior.
Influences polymorph formation and crystal habit.
Affects viscosity, heat transfer, and filtration.
Good solvent should provide:
High solubility at high T
Low solubility at low T
Good impurity rejection
Easy recovery (low boiling point)
94. How do you avoid oiling-out phenomenon?
Oiling-out = solute separates as an amorphous liquid phase instead of crystals.
Preventive measures:
Avoid excess supersaturation.
Use proper solvents / anti-solvents.
Control cooling rate.
Remove impurities that lower solubility.
Use seeding to guide crystallization.
95. What is zone refinement?
High-purity purification method based on melt crystallization.
A molten zone travels along the solid → impurities migrate with it.
Leaves behind highly pure crystalline material.
Used for metals, semiconductors, and pharmaceuticals.
96. What are mother liquor impurities?
Impurities dissolved in the liquid phase after crystallization.
Include: unreacted materials, by-products, solvent residues.
Affect crystal purity, habit, growth rate, and nucleation.
Managed by:
Purge stream
Mother liquor recycle optimization
Solvent change or treatment
97. Explain slurry viscosity measurement.
Slurry viscosity = resistance to flow in crystal–liquid mixture.
Measured using rotational viscometer, Brookfield viscometer, or inline sensors.
High viscosity → poor mixing, circulation, and heat transfer.
Controlled through temperature, solids loading, solvent selection.
98. What is a solubility plateau?
Region where solubility does not change significantly with temperature.
Problematic because cooling does not generate enough supersaturation.
Requires:
Anti-solvent addition
Vacuum evaporation
Solvent change
Important when designing cooling crystallization curves.
99. Why is filtration rate important?
Determines drying time, throughput, and downstream efficiency.
Affected by:
Crystal size
Crystal shape/habit
Mother liquor viscosity
Cake compressibility
Good filtration → lower moisture → faster drying → better quality.
100. What parameters affect filtration after crystallization?
Particle size distribution (PSD)
Crystal habit (shape)
Mother liquor viscosity
Solids loading (slurry density)
Cake thickness and compressibility
Presence of fines or agglomerates
Washing efficiency
Centrifuge or filter operating conditions
101. Why is crystallizer insulation required?
Prevents heat loss, ensuring a stable cooling profile.
Maintains constant supersaturation for controlled crystal growth.
Reduces energy consumption in chilled or heated crystallizers.
Prevents condensation and improves process safety.
102. Explain fouling factor.
Fouling factor = measure of resistance due to deposits on heat-transfer surfaces.
Higher fouling → lower heat transfer → higher energy cost.
Used in designing heat exchangers for crystallizers.
Indicates the need for cleaning frequency and maintenance.
103. What is the purpose of a reflux system in crystallizers?
Returns condensed vapors back to the crystallizer.
Maintains desired solvent composition and concentration.
Helps control evaporation rate, preventing excessive supersaturation.
Improves crystal purity by minimizing solvent losses.
104. Explain the concept of fractional crystallization.
Separates components based on differences in solubility.
Crystallizes one component selectively while the other remains dissolved.
Repeated cycles increase purity and separation efficiency.
Used for organic chemicals, salts, and pharmaceuticals.
105. What are typical control loops in crystallizers?
Temperature control loop → maintains cooling profile.
Level control loop → maintains slurry volume.
Vacuum control loop (for evaporative units).
Flow control (circulation, anti-solvent addition, feed).
Supersaturation monitoring using PAT tools.
Ensures steady PSD, yield, and crystal size.
106. Why is venting required in crystallizers?
Removes non-condensable gases from vapor space.
Prevents pressure buildup and foaming.
In evaporative units, ensures efficient boiling and heat transfer.
Protects equipment from vacuum or overpressure hazards.
107. What is purge filtration?
Removal of a small portion of slurry to control impurity buildup.
Purged solids and mother liquor are separated by filtration.
Prevents impurities from affecting crystal growth and purity.
Essential in continuous crystallization to maintain steady-state.
108. How to control nucleation rate?
Maintain supersaturation within metastable zone.
Use controlled cooling instead of rapid quenching.
Adjust seeding quantity and quality.
Reduce agitation intensity to limit secondary nucleation.
Remove impurities that act as nucleation sites.
109. Explain desupersaturation.
Process of reducing supersaturation by crystal growth.
Occurs when solute molecules deposit onto crystal surfaces.
Essential to stabilize crystallization after seeding.
Controlled by balance of cooling, feed concentration, and agitation.
Relation:
Desupersaturation Rate ≈ Crystal Growth Rate × Crystal Surface Area
110. How do you choose between cooling and evaporative crystallizer?
Choose cooling crystallizer when:
Solubility decreases sharply with temperature.
Product is heat-sensitive.
Solvent is expensive (no evaporation losses).
Choose evaporative crystallizer when:
Solubility is less temperature-dependent.
Large volumes require continuous crystallization.
Vacuum can be used to reduce boiling point.
High purity salts or bulk chemicals are needed.
111. Common design parameters for crystallizer selection.
Solubility behavior of solute vs. temperature.
Required crystal size distribution (CSD).
Heat sensitivity of product.
Impurity level and purity requirement.
Production capacity and batch vs continuous mode.
Viscosity and rheology of slurry.
Energy availability (vacuum, steam, chilled water).
Downstream requirements: filtration, drying, milling.
112. Explain solubility vs. temperature relationship.
Most solutes show increased solubility with temperature.
Cooling → supersaturation → crystallization.
Some materials show retrograde solubility (solubility decreases with heat).
Solubility curve helps determine:
Cooling rate
Optimal seeding point
Maximum achievable yield
113. What is the effect of pressure drop in crystallizers?
Influences evaporation rate in evaporative crystallizers.
High pressure drop → poor vapor removal → reduced supersaturation.
Can cause instability in vacuum crystallizers.
Affects circulation flow → impacts growth and nucleation rates.
Must be minimized for steady operation.
114. Explain slurry withdrawal mechanism.
Controlled removal of crystal-laden slurry from crystallizer bottom.
Ensures consistent residence time and PSD.
Uses valves, pumps, or elutriation legs.
Prevents blockages by maintaining proper velocity.
Must avoid removing excessive fines → affects product quality.
115. What is evaporative load?
Amount of solvent that must be evaporated to achieve desired supersaturation.
Higher evaporative load → higher energy consumption.
Depends on:
Feed concentration
Desired crystal yield
Solubility data
Important for sizing evaporators, condensers, and vacuum system.
116. How to avoid choked flow in crystallizer outlet?
Maintain adequate slurry velocity to prevent settling.
Optimize slurry density.
Use larger-diameter discharge lines.
Ensure proper agitation and circulation.
Install flush lines to dissolve deposits.
Avoid long stagnation zones where crystals can accumulate.
117. Why do we analyze crystal moisture content?
Impacts drying time and energy cost.
High moisture → poor flowability and risk of agglomeration.
Affects final purity, as mother liquor contains impurities.
Helps optimize centrifuge performance and washing efficiency.
Critical parameter in pharmaceutical API quality.
118. What is crystallizer yield loss and how to reduce it?
Yield loss = solute remaining in mother liquor or lost during handling.
Reduced by:
Lower final temperature (greater solute recovery).
Optimizing mother liquor recycle.
Better seeding strategy.
Reducing impurities that increase solubility.
Efficient filtration and washing.
119. What is the effect of anti-solvent addition rate?
Fast addition → high supersaturation → excessive nucleation → fines.
Slow, controlled addition → uniform growth and narrow PSD.
Addition rate controls:
Nucleation vs growth balance
Impurity rejection
Final crystal habit
Must be synchronized with mixing and temperature.
120. What process analytical technology (PAT) tools are used?
FBRM (Focused Beam Reflectance Measurement) – monitors chord length/PSD in real time.
PVM (Particle Vision & Measurement) – real-time imaging.
ATR–FTIR – monitors supersaturation via concentration.
Turbidity sensors – detect nucleation onset.
Temperature and conductivity probes – solubility and salt concentration tracking.
PAT ensures consistent quality, controlled nucleation, and reproducible batches.