Process for purification and separation of cannabinoids, from dried hemp and cannabis leaves
A method for purification and separation of cannabinoids, such as cannabidiol and tetrahydrocannabinol, e.g., from the dried hemp and cannabis leaves can use a continuous simulated moving bed process and a combination of one or more of a sequence of purification steps including: filtration, decolorization, activation or decarboxylation, dewaxing, polishing, and crystallization to separate a cannabinoid from the cannabis plant and to provide various cannabinoid products. The cannabinoid products can be used in various pharmaceutical and nutraceutical applications.
1. A method of separating a cannabinoid from a cannabis plant, the cannabis plant including the cannabinoid and at least one impurity, the method comprising:
combining the cannabis plant and a solvent to form a crude cannabis extract stream;
processing the crude cannabis extract stream into a simulated moving bed (SMB) feedstock stream by removing at least a portion of at least one impurity in the crude cannabis extract stream; and
passing the SMB feedstock stream through a SMB zone to provide a primary raffinate stream having a higher purity of the cannabinoid than in the SMB feedstock stream as measured by weight percentage of the solid content and a SMB extract stream having a lower purity of the cannabinoid than in the SMB feedstock stream as measured by weight percentage of the solid content.
2. The method of claim 1 , wherein the cannabis plant is selected from Cannabis sativa, Cannabis indica, Cannabis rudralis , and mixtures thereof.
3. The method of claim 1 , wherein the cannabis plant comprises dried hemp, cannabis leaves, or a mixture thereof.
4. The method of claim 1 , wherein the solvent comprises ethanol.
5. The method of claim 1 , wherein said at least one impurity comprises at least one of color bodies, acidic components, lipids, and cannabis plant waxes, and wherein processing the crude cannabis extract stream includes at least one of decolorizing the crude cannabis extract stream to remove at least a portion of the color bodies from the crude cannabis extract stream, activating the crude cannabis extract stream to remove at least a portion of the acidic components from the crude cannabis extract stream, and dewaxing the crude cannabis extract stream to remove at least a portion of the lipids and cannabis plant waxes from the crude cannabis extract stream.
6. The method of claim 5 , wherein processing the crude cannabis extract stream into the SMB feedstock stream includes passing the crude cannabis extract stream through a first chromatographic resin, and passing the SMB feedstock stream through the SMB zone includes passing the SMB feedstock stream through a second chromatographic resin, the second chromatographic resin being different from the first chromatographic resin.
7. The method of claim 1 , wherein the SMB zone comprises a plurality of adsorbent beds, each bed containing a modified hydrophobic adsorbent comprising a poly(methyl methacrylate) (PMMA) resin or a styrene-divinylbenzene (DVB) resin having 4 percent to 8 percent crosslinking.
8. The method of claim 7 , wherein the plurality of adsorbent beds are arranged in serial fluid communication such that fluid introduced at a top of any adsorbent bed (n) passes to the next highest adsorbent bed (n+1).
9. The method of claim 8 , further comprising:
advancing each adsorbent bed, such that adsorbent bed n+1 becomes adsorbent bed n after advancing, and adsorbent bed n prior to advancing becomes adsorbent bed n+x after advancing, wherein adsorbent bed n+x is the highest adsorbent bed in the serial fluid communication arrangement.
10. The method of claim 8 , wherein there are eight adsorbent beds in a 2-3-2-1 arrangement, wherein two adsorbent beds are operated in a desorption zone, three adsorbent beds are operated in a rectification zone, two adsorbent beds are operated in an adsorption zone, and one adsorbent bed is operated in a concentration zone, respectively.
11. The method of claim 1 , wherein the cannabinoid is cannabidiol (CBD).
12. The method of claim 11 , wherein said at least one impurity of the crude cannabis extract stream comprises a second cannabinoid selected from cannabidiolic acid (CBDA), cannabigerol (CBG), cannabinol (CBN), tetrahydrocannabinol (THC), tetrahydrocannabinolic acid (THCA), and combinations thereof.
13. The method of claim 11 , wherein said at least one impurity of the crude cannabis extract stream comprises tetrahydrocannabinol (THC), and wherein the primary raffinate stream is essentially free of THC.
14. The method of claim 13 , wherein the average mass recovery of CBD in the primary raffinate stream is 80 wt. % or more.
15. The method of claim 13 , wherein the CBD of the primary raffinate stream has an average purity of 35% to 50% as determined by HPLC.
16. The method of claim 13 , further comprising:
evaporating the primary raffinate stream to provide a cannabinoid oil stream.
17. The method of claim 16 , further comprising:
mixing the cannabinoid oil stream with a non-polar solvent to provide a polishing zone feed stream;
agitating the polishing zone feed stream for a first period of time;
allowing the agitated polishing zone feed stream to settle for a second period of time; and
filtering the settled polishing zone feed stream to provide a filtered non-polar solution having a higher purity of the cannabinoid than in the cannabinoid oil stream as measured by weight percentage of the solids content.
18. The method of claim 17 , further comprising:
evaporating the filtered non-polar solution to provide an evaporated cannabinoid oil stream.
19. The method of claim 18 , further comprising:
washing the evaporated cannabinoid oil stream with a wash solvent to provide a washed cannabinoid oil stream.
20. The method of claim 19 , wherein washing the evaporated cannabinoid oil stream includes washing the evaporated cannabinoid oil stream more than once.
21. The method of claim 19 , wherein the wash solvent comprises methanol, water, or mixtures thereof.
22. The method of claim 19 , further comprising:
drying the washed cannabinoid oil stream.
23. The method of claim 22 , wherein the washed cannabinoid oil stream is THC free.
24. The method of claim 17 , further comprising:
passing at least a portion of the filtered non-polar solution through an isolate chromatography zone comprising a first chromatography column and a second chromatography column to provide an isolate elute stream having a higher purity of the cannabinoid than in the filtered non-polar solution as measured by weight percentage of the solid content, wherein the first and second columns are connected in serial fluid communication.
25. The method of claim 24 , wherein the first chromatography column comprises a hydrophilic resin comprising a spherical polar silica adsorbent having Si—OH groups, an average particle diameter between 60-200 microns, a surface area between 450-550 m 2 /g, a pore volume of between 0.7-0.85 mL/g, and a pore size between 0.005-0.0075 microns.
26. The method of claim 25 , wherein the second chromatography column comprises an activated alumina adsorbent having an average particle diameter between 50-200 microns, an average bulk density of 0.85 g/mL, a surface area between 140-170 m 2 /g, and an average pore diameter greater than 0.006 microns.
27. The method of claim 24 , further comprising:
cooling the isolate elute stream for a cooling period of time, to thereafter provide crystallized cannabidiol.
28. The method of claim 27 , wherein the crystallized cannabidiol has a purity of about 96 wt. % to about 98 wt. % as determined by HPLC.
29. The method of claim 27 , further comprising:
recrystallizing the crystallized cannabidiol.
30. The method of claim 29 , wherein the recrystallized cannabidiol has a purity of greater than 99 wt. % as determined by HPLC.