Case Study - Elevating Purity Levels: Racemizing Pharmaceutical Products in Advanced Flow Microreactors

Racemization involves transforming an optically active compound into its racemic (optically inactive) counterpart through either heat or a chemical reaction. This results in an equal 1:1 ratio of enantiomers, forming what is known as a racemic mixture. Typically, reactions are specific to one stereoisomer, leading to the desired product, while the other stereoisomer remains unreactive or might trigger undesired side effects.

The Project:

To perform racemization of an unwanted compound to achieve a biologically active racemic mixture with high purity. The project involved two stages: initial experimentation in a batch system to identify and understand the challenges faced, and subsequent implementation in a flow system. The transition to the flow system served a dual purpose – addressing challenges encountered in the batch setup and enabling the scalability of the process for large-scale production of the compound while maintaining the purity.

About the client:

The client is a biotechnology company headquartered in the United States, specializing in drug research and development especially focusing on creating innovative small-molecule therapies for immune-inflammatory conditions.

Aragen’s Approach:

Batch experiments: Undesired compound was taken in 15 vol. of toluene and heated to reflux for 5-6 hrs.

Issue in batch racemization: Due to longer exposure under reflux conditions purity of compound decreased from 99.7% to 92% as indicated by HPLC analysis.

Project outcome:

• Complete racemization achieved at temperature 180°C and residence time of 5.4 min.
• Compound purity remains above 99.5%, attributed to the less exposure time in flow reactor.
• Continuous outlet stream of racemized reaction mass can be connected to a separation unit.
• Operation at 180°C was compensated by back pressure regulator to avoid any boiling of solvent.

Aragen Advantage:

• Availability of a range of advanced microreactors with varying channel dimensions.
• Tubular flow crystallizer with mixing by design
• Fixed Bed Reactor (up to 250 mL fixed bed column)
• Greener approach with capabilities encompassing screening, lab development and piloting
• Capability to process multi kilograms scale (up to 5-10 Kg)
• Dedicated team of experts for flow process development
• Strong collaboration with leading flow reactor vendors
• Proven track record in technical problem-solving for leading global pharma and biotech companies To know more about our flow chemistry expertise or to speak with our subject experts, write to us at bd@aragen.com.