What minimum amount of API is needed to start a crystallization development project?

The required amount depends on the scope of solid-form screening and process optimization. Typically, gram-scale material is sufficient for initial thermodynamic and kinetic studies, but the exact quantity is scoped during consultation based on the target design space.

How do you handle metastable polymorphs during scale-up?

We apply specialized strategies that control supersaturation, seeding, and temperature to maintain the metastable form. Process conditions are optimized to avoid conversion to more stable forms, and PAT is used to confirm polymorphic purity in real time during scale-up runs.

Can crystallization be used for chiral resolution?

Yes, crystallization can be an economical route to enantiomerically pure material via diastereomeric salt formation or preferential crystallization of conglomerates. The feasibility and method are evaluated case-by-case during the scoping phase.

Do you offer real-time monitoring using Process Analytical Technology (PAT)?

Yes, we integrate in-line or at-line PAT tools such as Raman spectroscopy, focused beam reflectance measurement (FBRM), and particle vision measurement (PVM) to monitor solid form, particle size, and nucleation events in real time, enabling process control and characterization.

What deliverables are provided after project completion?

You receive a full process development report including solid-form characterization data, solubility and MSZW measurements, DoE results, scale-up risk assessment, and a transfer-ready process description with identified CPPs, CQAs, and failure modes. PAT data and analytical methods are also provided.

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Crystallization Process Development and Optimization

Process Development

Transform solid-form selection into a reproducible, scalable manufacturing process with QbD-driven design of cooling, antisolvent, and reactive crystallization.

Polymorph control and metastable form stabilization
Particle engineering for size, shape, and flow properties
Design space mapping via hybrid modeling and DoE
Scale-up risk assessment and process-transfer support

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Why partner with us for crystallization development?

Our approach connects thermodynamic understanding with process engineering to deliver robust crystallization processes that meet your target product profile.

Solid-form control from selection through manufacturing
Scalable QbD-driven process design
Seeding and supersaturation control for consistent particle attributes
Integration of PAT for real-time process monitoring

Reproducible

Scalable

QbD-driven

Our Approach

Systematic Process Design from Molecule to Manufacturing

We harmonize solid-form characterization, thermodynamic and kinetic parameter determination, and process-level risk assessment to design crystallization processes that consistently deliver intended form, purity, and particle attributes.

Integrated Process Design

Our integrated approach combines solid-form selection, thermodynamic and kinetic characterization, and QbD principles to define the design space and establish robust control strategies for reproducible crystallization at scale.

Polymorph, hydrate, solvate, and salt mapping via XRPD, DSC, TGA
Solubility and metastable zone width determination
Seeding strategy development and supersaturation profile optimization

Scale-Up and Technology Transfer

We translate lab-scale processes to pilot and commercial scales with quantitative risk assessment, mixing studies, and PAT integration to ensure consistent performance and material attributes across equipment configurations.

Scale-up risk assessment and heat/mass transfer evaluation
Design of Experiments (DoE) for critical process parameter characterization
Process analytical technology (PAT) integration for real-time monitoring

Quality by Design

Critical process parameters and quality attributes are systematically identified to define the design space and establish robust control strategies for reproducible manufacturing.

Metastable Polymorph Control

Specialized strategies are applied to control metastable forms, optimizing process conditions to ensure stability and reproducibility at scale while avoiding undesired phase transformations.

Particle Engineering

By controlling nucleation and growth kinetics, we engineer particle size, morphology, and surface properties to meet downstream requirements for filtration, flow, dissolution, and drug-product performance.

Deliverables

Comprehensive Data and Transfer-Ready Documentation

Every project delivers a full process development report, solid-form characterization data, and a transfer-ready package that documents CPPs, CQAs, failure modes, and scale-up guidance.

Data and Characterization

Solid-form analysis (XRPD, DSC, TGA, microscopy, particle size)
Solubility and metastable zone width data across relevant solvents
Impurity profiling and chemical purity confirmation
Process analytical data from in-line PAT measurements

Process Recommendation and Support

Transfer-ready process description with identified CPPs and CQAs
Failure mode and effect analysis (FMEA) for process risks
Scale-up recommendation including mixing, heat transfer, and equipment considerations
Support for technology transfer and process validation

Service Scope

Tailored to Your API and Target Product Profile

Each engagement is scoped collaboratively based on the solid-form landscape, development stage, and commercial scale requirements. Parameters and depth are defined in the project SOW.

Parameter	Typical Project Scope
Solid-Form Selection	Polymorph, hydrate, solvate, and salt screening; thermodynamic ranking via competitive slurries; orthogonal characterization (XRPD, DSC, TGA)
Solvent / Antisolvent Screening	Solubility measurement across solvent systems; antisolvent selection; assessment of effect on polymorph and particle attributes
Seeding Strategy	Seed preparation, size, loading, and addition point optimization; impact on polymorphic purity and particle size distribution
Cooling / Antisolvent Profile	Linear, stepwise, and programmed cooling profiles; antisolvent addition rate optimization; supersaturation control via DoE
Scale-Up Study	Pilot-scale demonstration with mixing assessment; heat/mass transfer evaluation; risk assessment for equipment geometry and scale factors
PAT Integration	In-line or at-line monitoring (Raman, FBRM, PVM) for real-time solid-form and particle size tracking; data for process control and validation

Workflow

A Structured Path from Molecular Understanding to Robust Manufacturing

Our workflow systematically connects solid-form selection, thermodynamic and kinetic characterization, and QbD-based optimization to deliver a transfer-ready crystallization process.

Solid-Form and Solvent System Selection

Identify the target polymorph, hydrate, or solvate; screen solvent systems and determine solubility profiles; select precipitating agent and preliminary operating conditions.

Thermodynamic and Kinetic Characterization

Measure metastable zone width (MSZW) and nucleation induction times under multiple conditions; determine crystal growth rates and Ostwald ripening behavior.

Process Parameter Optimization

Apply QbD and Design of Experiments (DoE) to optimize cooling rate, antisolvent addition profile, seeding parameters, and agitation to achieve target particle size, morphology, and polymorphic purity.

Scale-Up Demonstration

Execute process at pilot scale with in-line PAT monitoring; assess mixing, heat transfer, and mass transfer effects; adjust parameters to maintain consistency with lab-scale outcomes.

Process Characterization and Transfer

Define critical process parameters (CPPs) and critical quality attributes (CQAs); map design space; compile process transfer package with risk assessment and scale-up guidance.

Applications

Solving Downstream Development Challenges with Precise Crystallization Control

Our crystallization process development addresses a wide range of solid-state and particle engineering needs, from polymorph control to impurity rejection.

Reliable production of the desired polymorph every time

Achieve robust control over polymorphic form and avoid unwanted hydrates, solvates, or amorphous material during scale-up and manufacturing.

Seeding and supersaturation control for polymorphic purity
Metastable form stabilization through process parameter optimization

Tailored particle size, shape, and surface properties

Design crystallization conditions to produce particles with defined size distribution, morphology, and flow characteristics for downstream processing and final drug product performance.

Improved filtration and drying efficiency
Enhanced dissolution rate and bioavailability

Clear process impurities through selective crystallization

Leverage differences in solubility and crystal lattice to reject process-related impurities, improving chemical purity without additional chromatography steps.

Impurity rejection profiling and yield optimization
Residual solvent reduction to below ICH limits

FAQ

Frequently Asked Questions About Crystallization Process Development

Find answers to common questions about our approach, deliverables, and project engagement.

The required amount depends on the scope of solid-form screening and process optimization. Typically, gram-scale material is sufficient for initial thermodynamic and kinetic studies, but the exact quantity is scoped during consultation based on the target design space.
We apply specialized strategies that control supersaturation, seeding, and temperature to maintain the metastable form. Process conditions are optimized to avoid conversion to more stable forms, and PAT is used to confirm polymorphic purity in real time during scale-up runs.
Yes, crystallization can be an economical route to enantiomerically pure material via diastereomeric salt formation or preferential crystallization of conglomerates. The feasibility and method are evaluated case-by-case during the scoping phase.
Yes, we integrate in-line or at-line PAT tools such as Raman spectroscopy, focused beam reflectance measurement (FBRM), and particle vision measurement (PVM) to monitor solid form, particle size, and nucleation events in real time, enabling process control and characterization.
You receive a full process development report including solid-form characterization data, solubility and MSZW measurements, DoE results, scale-up risk assessment, and a transfer-ready process description with identified CPPs, CQAs, and failure modes. PAT data and analytical methods are also provided.

Scientific Literature

References

Nandi S, Padrela L, Tajber L, et al. Development of long-acting injectable suspensions by continuous antisolvent crystallization: An integrated bottom-up process. International journal of pharmaceutics. 2023;648:123550. View on PubMed
Szilágyi B. Mathematical Modeling. Advances in biochemical engineering/biotechnology. 2026 Mar 13. View on PubMed
Chaverra-Muñoz L, Briem T, Hüttel S. Optimization of the production process for the anticancer lead compound illudin M: downstream processing. Microbial cell factories. 2022;21(1):165. View on PubMed

Please kindly note that our products and services are for research use only.