Integrated Extraction and Purification of High-Purity Cannabidiol from Industrial Hemp: Continuous Chromatography and Scale-Up Considerations

Cannabidiol (CBD) is a high-value non-psychoactive constituent of industrial hemp with diverse pharmacological activities. However, its low natural abundance, poor thermal stability, and the difficulty in removing psychoactive Δ9-tetrahydrocannabinol (THC) limit the efficient and scalable preparation of high-purity CBD. Although recent reviews cover the cannabis processing chain or chromatographic isolation, a systematic and quantitative comparison of extraction and downstream purification as an integrated workflow is still lacking. This review establishes an integrated comparative framework for producing high-purity CBD from industrial hemp. Conventional solvent extraction, supercritical fluid extraction, physical field-assisted extraction, and green solvent extraction are compared. Mainstream purification approaches, including molecular distillation, chromatography, and crystallization, are discussed, with emphasis on continuous chromatographic strategies such as simulated moving bed (SMB) and recycling chromatography, alongside a critical assessment of their current laboratory/preparative-scale validation and scale-up feasibility. The analysis shows that no single technique can simultaneously balance efficiency, purity, and cost; multi-technology coupling is a promising strategy for future industrial translation. Future research should focus on continuous chromatography, green solvents, process integration, and intelligent manufacturing to bridge the gap between laboratory validation and scalable industrial production.