(179a) Solubiltiy and Phase Equilibria for Optimizing the Processing of Cannabinoids and Terpenes in Cannabis and Hemp Extractions

The extraction and processing of the components associated with medicinal cannabis and hemp extracts is rather daunting since cannabis plant materials can have in excess of 400 molecular compounds. Two molecular groups consisting of 12 major cannabinoids and 10-15 terpenoids components are of particular interest and the focus of using pressurized fluid extractions for their processing. Pressurized fluids such as carbon dioxide and butane coupled with conventional liquid solvents such as ethanol and water are routinely used to produce cannabis concentrates in which the pressurized fluid is used in both the sub- as well as the supercritical state (CO₂), or as a near critical fluid in the case of butane. Optimization of extraction and fractionation conditions is difficult due to the lack of fundamental thermodynamic solubility data and phase equilibria. Sources of useful data have been employed toward this end using extraction data available for essential oil components in liquefied- and supercritical- carbon dioxide as well as the meager literature data available at lower pressures (<200 bar) for important cannabinoids such as cannabinol (CBD ) and tetrahydrocannabinol (THC). Solubility data from the Delft study show that CBD and THC solubility increases with pressure, differentially for the major cannabinoid components allowing for their fractionation at these low pressures as well as exhibiting the “crossover region” between 110-140 bar and 40-60^oC^.  Solubility parameter theory has also been employed to rationalize experimental extraction data by using group contribution calculations based on the molecular structure of the major cannabinoid and terpene components for both critical fluids and liquid solvent media - particularly with respect to their sequential use in extractions in both the near critical and supercritical state. For the major cannabinoid components found in cannabis and hemp extracts, solubility parameter theory predicts solubility maximum occurring to occur at quite high extraction pressures equivalent to solubility parameters of 22-25 MPa^1/2, or equivalent to the solubility parameter of ethanol. Many of the difficult to isolate terpenoid components show solubility minimum in CO₂ at 80-90 bar and 60^oC (limonene and beta-carophyllene) and their solubility increases in both sub- and supercritical CO₂ with both an increase or decrease in temperature. At higher extraction pressures and temperatures in CO₂, terpenoids should exhibit solubility maxima at lower pressures than those for the acidic and neutral cannabinoid compounds, thereby permitting the fractionation at either subcritical or supercritical CO₂ conditions. Major terpenoid components such as beta-carophyllene found in cannabis can be fractionated from plant wax material optimally below 40^oC and a CO₂ pressure of 90 bar since the wax components exhibit a solubility maxima under these conditions. Separator conditions can be adjusted between 30-70 bar and 0-40^oC to separate the essential oil components, i.e., the terpenes from the plant wax material The presence of water in the plant material can also influence the terpenoid composition in the resultant extract at conditions close to P_c of CO₂ and the temperature range of 40-50^oC. Aside from predicting optimal extraction conditions for cannabinoid and terpene constituents, the above approaches will also be used along with equation-of-state calculations for selecting conditions for precipitation of these solutes in separator vessels as commonly employed in processing of cannabis and hemp extracts. In the case of the cannabinoid components, CBD, delta-8-THC, and delta-9-THC, both sub- and super-critical CO₂ conditions are used for the adjustment of precipitation conditions in separator vessels between 29-50^oC and 55-70 bar. An example of the sequential extraction of terpenes and cannabinoids from cannabis using subcritical (69 bar/26^oC) and supercritical (240 bar/40-45^oC) CO₂ will be shown, and conditions suggested for stripping ultra-low levels of pesticides from cannabis and hemp matrices.