Development of an SMB process for the purification of CBD from a CBD-rich cannabis extract

Importance of the topic

Efficient removal of cannabidiol from plant extracts is a growing concern in natural product purification. Conventional batch chromatography and distillation require high energy and solvent usage and often yield limited throughput. Simulated moving bed chromatography offers a continuous approach that reduces solvent consumption and processing times while delivering high purity and recovery rates.

Objectives and study overview

This work aimed to design and optimize an SMB process for isolating cannabidiol from a CBD rich cannabis extract. The goals were to achieve high daily throughput, maximize CBD recovery, and ensure product purity above 90 percent. Key steps included sample pretreatment, SMB parameter determination, and process evaluation under different configurations.

Methodology and instrumentation

Sample preparation involved filtration and a pre preparative step using a semi preparative C18 column operated with ethanol to remove late eluting phytochemicals. The purified fraction was concentrated by rotary evaporation and diluted prior to analysis. Analytical retention times for CBD and related cannabinoids were measured on nine identical C18 columns to ensure uniform performance. SMB start parameters were calculated with dedicated software applying triangle theory and linear adsorption isotherms. Four process variants were tested in both open and closed loop modes, adjusting feed flow, switching time and sample concentration to identify optimal conditions.

Instrumentation

• Preparative HPLC system with dual AZURA pumps, variable wavelength UV detector, fraction waste valve and C18 column (150 x 50 mm)
• AZURA Lab SMB platform with four stainless steel zone pumps, feed pump, dual UV detectors, Coriolis flow meters, eight C18 columns (250 x 8 mm), and PurityChrom MCC software
• Rotary evaporator for sample concentration

Key results and discussion

Initial sample contained 35.9 mg/ml of CBD and was reduced to 4.3 mg/ml after preparative cleanup and to 8.3 mg/ml by half evaporation. The volume overload study confirmed linear adsorption up to 100 microliter injection. In open loop mode (method MO2), SMB yielded 42 mg of CBD per cycle at 89 percent recovery and 93 percent purity after four cycles. Transition to closed loop provided solvent recycling but required trade offs between recovery and purity. Increasing feed concentration to 20.5 mg/ml doubled CBD output to 95 mg per cycle with 81 percent recovery and stable purity. Daily productivity reached nearly two grams of CBD with optimized sample concentration.

Benefits and practical applications

The developed SMB method delivers continuous purification of cannabidiol with lower solvent use and higher throughput than batch alternatives. Its flexibility allows tuning of operating parameters for target recovery and purity profiles. The approach is well suited for pharmaceutical grade CBD production as well as fine chemical applications requiring large scale continuous separation.

Future trends and potential applications

Further advancements may include integration of inline spectroscopic monitoring for real time process control, application of greener solvents to improve sustainability, and adaptation to other minor cannabinoids or complex natural extracts. Scale up of SMB operations could support continuous manufacturing frameworks in the nutraceutical and pharmaceutical industries.

Conclusion

This study demonstrates that simulated moving bed chromatography can efficiently isolate cannabidiol from a complex plant matrix. By optimizing sample preparation, column uniformity and SMB parameters, high daily yields with recovery above 80 percent and purity over 90 percent were achieved. The method offers a scalable, eco friendly alternative to conventional batch purification.

References

• Blanc CL et al. Purification of organic acids by chromatography: Adsorption isotherms and impact of elution flow rate. Sep Purif Technol. 2015.
• Rajendran A et al. Simulated moving bed chromatography for the separation of enantiomers. J Chromatogr A. 2009.
• Rodrigues AE et al. Simulated Moving Bed Technology: Principles, Design and Process Applications. Butterworth Heinemann. 2015.
• Seidel-Morgenstern A et al. New Developments in Simulated Moving Bed Chromatography. Chem Eng Technol. 2008.
• Loxterkamp L, Monks K. Determination of sixteen cannabinoids inside flowers, oils and seeds. KNAUER. 2020.