Background
The global cannabis market has experienced remarkable growth, driven mainly by the rising demand for cannabinoid-based products and the legalisation of cannabis across the globe. Therefore, the cannabis industry has prioritised the development of sustainable and effective extraction processes. Several extraction technologies have been used. Traditional methods rely on volatile organic solvents such as hexane, ethyl acetate, or chloroform [1], which are not eco-friendly and not selective [2]. Green alternatives such as ionic liquids, deep eutectic solvents and bio-based solvents have been explored but face challenges such as high costs and scalability issues [3].
Liquid-liquid extraction (LLE) provides an alternative method for extracting cannabinoids from cannabis. This approach offers several benefits, including simplicity, low investment costs and energy consumption, and environmental friendliness [2, 4, 5]. The process involves four main stages: leaching, extraction, stripping, and precipitation [2]. Our previous research indicates that pH-controlled aqueous solvents are effective for leaching cannabinoids, particularly in their acidic forms [2]. However, several factors should be optimised in the leaching process to obtain the highest yield and efficiency.
This study evaluated different initial forms of cannabis flowers and various leaching parameters, including solvent pH, solid-to-liquid ratio, leaching time and temperature on cannabinoid leaching efficiency. Additionally, key kinetic and thermodynamic parameters were determined to provide a comprehensive understanding of the leaching process using a pH-controlled aqueous solvent.
Method
Different forms of cannabis flowers (whole and ground, fresh and dry) were leached using methanol (as a reference solvent) and pH-controlled aqueous solvent. Ultrasound- and agitation-assisted leaching methods were utilised. The concentrations of cannabinoids in leachate were analysed using Ultra-High-Performance Liquid Chromatography-Mass Spectrometry (UHPLC-MS) to determine the optimal leaching conditions.
Results
Whole fresh cannabis flowers are the most effective starting material for cannabinoid leaching. Grinding dried cannabis flowers did not improve cannabinoid yield. The alkaline aqueous solution can efficiently leach cannabinoids from cannabis, especially their acidic forms. However, very high alkaline conditions can degrade cannabinoids.
Peleg’s model accurately predicts (R2 ≥ 0.98) cannabinoid leaching behaviour in pH-controlled aqueous solvents. A short leaching time (~10 min) is required for all flower forms and grinding reduced this duration.
Leaching cannabis at temperatures above 35ºC is not recommended, as it may degrade or decarboxylate cannabinoids. Thermodynamic analysis showed that cannabinoid leaching with this solvent is an exothermic and spontaneous process.
Conclusion
In conclusion, alkaline solvents effectively leach cannabinoids from cannabis, with whole fresh flowers being the ideal starting material. A short leaching time is needed, and the process is both spontaneous and exothermic, though high alkalinity or temperatures over 35ºC may cause the degradation of cannabinoids.
References
[1] C. L. Ramirez, M. A. Fanovich, and M. S. Churio, "Cannabinoids: Extraction methods, analysis, and physicochemical characterization," in Studies in natural products chemistry, vol. 61: Elsevier, 2019, pp. 143-173.
[2] H. T. Lu et al., "Green method for recovery of cannabinoids from Cannabis sativa flowers: pH-controlled aqueous leaching," Separation and Purification Technology, vol. 326, p. 124754, 2023, doi: https://doi.org/10.1016/j.seppur.2023.124754.
[3] C. López-Olmos, M. T. García-Valverde, J. Hidalgo, C. Ferrerio-Vera, and V. Sánchez de Medina, "Comprehensive comparison of industrial cannabinoid extraction techniques: Evaluation of the most relevant patents and studies at pilot scale," Frontiers in Natural Products, vol. 1, 2022, doi: https://doi.org/10.3389/fntpr.2022.1043147.
[4] W. Li, H. T. Lu, M. S. Doblin, A. Bacic, G. W. Stevens, and K. A. Mumford, "A solvent loss study for the application of solvent extraction processes in the pharmaceutical industry," Chemical Engineering Science, vol. 250, p. 117400, 2022, doi: https://doi.org/10.1016/j.ces.2021.117400.
[5] S. Tshepelevitsh et al., "Systematic Optimization of Liquid–Liquid Extraction for Isolation of Unidentified Components," ACS Omega, vol. 2, no. 11, pp. 7772-7776, 2017, doi: https://doi.org/10.1021/acsomega.7b01445.
Acknowledgement: The authors would like to acknowledge the funding provided by the Australian Research Council to the Industrial Transformation Research Hub for Medicinal Agriculture (ARC MedAg Hub, IH180100006), a Linkage Program grant (LP160101317), and the Australian Department of Education Regional Research Collaboration Program – Next Generation Protected Cropping in a Regional Manufacturing Facility. We would also like to thank Cann Group Ltd. (Victoria) for providing the cannabis material for this project.