Tetrahydrocannabinol separation from cannabis extracts using centrifugal partition chromatography

In this study, a method was developed for the separation of tetrahydrocannabinol (THC) from a Cannabis extract to obtain a THC-free product that meets regulatory and commercial specifications for large-scale production. Considering Colombia's regulations and pharmaceutical restrictions on certain solvents, heptane, ethanol, and water were selected for this study. Process simulation software (ASPEN Plus V14) was used to generate a ternary phase diagram and identify suitable solvent systems for the separation of THC from cannabis extract. In this diagram, the biphasic (liquid-liquid) region was determined, and within it, the low-polarity zone (characterized by low water content) was delineated. Four heptane/ethanol/water (HEtWat) solvent systems were preselected: I: 4.6/3.5/1, II: 7.2/5.6/1, III: 16.2/10.4/1, and IV: 4/4/1 (v/v/v). These systems were evaluated based on the THC partition coefficient (K_THC). Two solvent systems were selected for laboratory-scale tests using a Gilson CPC 250 unit. Among them, the heptane/ethanol/water system 4.6/3.5/1 (v/v/v) was chosen for method development at industrial scale using a Rothacrom rCPC system. Additionally, two laboratory-scale tests demonstrated the method's viability to: (1) separate THC from mother liquor (a byproduct resulting from the crystallization of cannabidiol (CBD)) yielding a THC-free product enriched in minor cannabinoids (a key feature of mother liquor); and (2) purify THC from a refined extract (distillate) enriched in this cannabinoid. several tests was performed to determine the maximum mass of full-spectrum (FS) Cannabis extract that could be processed, achieving sufficient THC separation to comply with regulatory limits (THC < 0.05 %). The process yielded 613 g of THC-free extract, referred to as broad spectrum (BS), containing 85 % CBD and 0.02 % THC, from 800 g of FS in 9.5 h, resulting in an operational efficiency of 77 % (613 g BS / 800 g FS). A total of 97.06 % of cannabichromene (CBC) was recovered in the residual fraction, indicating strong retention of this cannabinoid by the stationary phase. Fractions 9 and 10 contained 85.3 % (w/w) THC. These THC- and CBC-rich fractions are proposed for further isolation and potential applications in medical research.