[WEBINAR] Optimizing Diastereomeric Salt Crystallization for Enantiomer Separation

In this on-demand webinar, APC explores how Crystallization-Induced Diastereomeric Transformation, or CIDT, can improve diastereomeric salt crystallization for chiral resolution.

The session focuses on practical challenges in resolving double salts, including solubility behavior, phase relationships, counterion selection, solvent choice, and solid-state control. It also examines how targeted analytical insight can support higher selectivity, improved yield and purity, and more scalable routes to enantiopure compounds.

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Simon, M., Shortt, S., Burke, C., Bourke, E., Umerska, A., Jacob, A., Davin, S. and Glennon, B. (2025), Resolution of Double Salts via Crystallization-Induced Diastereomeric Transformation (CIDT). Chem. Eng. Technol., 48: e70056. https://doi.org/10.1002/ceat.70056

Why Enantiomer Separation Matters in Pharma Development

For chiral molecules, enantiomer separation is often a critical part of pharmaceutical process development. The desired enantiomer can define the safety, efficacy, and quality profile of a medicine, making resolution strategy an important CMC decision.

Diastereomeric salt crystallization remains a widely used and practical approach for enantiomer separation. The method relies on differences in solubility between diastereomeric salts, allowing one form to crystallize preferentially under defined process conditions.

While the underlying approach is straightforward, the outcome often depends on how these variables interact. Solvent choice, counterion selection, temperature, phase behavior, solid-state form, and crystallization conditions can all influence purity, yield, and scalability.

When these factors are not well understood, teams may face inconsistent resolution, difficult filtration, yield loss, unexpected solid forms, or crystallization behavior that does not translate cleanly from lab to scale.

Enantiomer Separation Through Diastereomeric Salt Crystallization

For chiral molecules, enantiomer separation can be a defining part of pharmaceutical process development. The selected resolution strategy affects purity, yield, material use, scalability, and the strength of the CMC package.

Diastereomeric salt crystallization remains a practical approach because it uses differences in salt solubility to separate the desired enantiomer. The challenge is that these systems are rarely controlled by one variable. Solvent, temperature, counterion, phase behavior, and solid form can all change the outcome.

That is especially important when working with double salts. A screen may identify a promising condition, but without a clear understanding of the phase behavior, teams can still face inconsistent resolution, yield loss, poor filtration, or scale-up issues.

Moving Beyond Empirical Screening

Screening is often the starting point for chiral resolution. It can identify potential resolving agents, solvents, and operating conditions. But screening alone does not always explain why a system works, where it is vulnerable, or how it will behave as the process is scaled.

This webinar looks at how solubility data, phase behavior, solid-state analysis, and process understanding can be used together to improve diastereomeric salt crystallization. The goal is not only to find a separation. It is to understand the system well enough to control it.

The Role of CIDT

Crystallization-Induced Diastereomeric Transformation uses crystallization conditions to drive transformation toward the desired diastereomeric salt.

For difficult resolutions, CIDT can create a route to better selectivity and recovery. Its success depends on understanding the relationship between solution behavior, solid-state form, and crystallization conditions. In practice, solvent choice and temperature profile often determine whether the transformation proceeds as intended and how efficiently the desired salt can be isolated.

What this Webinar Covers

• Mastering enantiomer separation through crystallization. Learn how diastereomeric salt crystallization uses solubility differences to support effective enantiomer resolution, and why phase behavior is central to resolving double salts.

• Optimizing yield and purity. Explore how solvent, temperature, and counterion selection influence crystallization efficiency, selectivity, impurity rejection, and material recovery.

• Scaling for industrial use. Understand what needs to be controlled for diastereomeric salt crystallization to support cost-effective enantiopure compound production beyond the initial screen.

From Resolution to Process Understanding

Successful chiral resolution is not just about identifying a workable condition. The real challenge is understanding how the system behaves, what controls the separation, and whether those same results can be reproduced and maintained as development progresses.

For teams developing chiral compounds, that means asking the right questions early:

• Can the desired enantiomer be isolated at the required purity?

• What conditions control selectivity and recovery?

• Are the relevant solid forms understood?

• How sensitive is the system to solvent, temperature, and counterion choice?

• Will the crystallization behavior hold as the process scales?

APC brings together crystallization science, process engineering, solid-state understanding, and analytical capability to help teams answer those questions earlier in development.