Pharmaceutical composition and method of manufacturing
View Patent ↗The present invention provides for methods of obtaining an extract of Cannabis plant material as well as subsequent processing of the extract to provide a concentrate of Cannabis . The present invention also provides for pharmaceutical dosage forms (e.g., oral thin films and transdermal patches) that include the concentrate (or extract) of Cannabis , as well as methods of medical treatment that include administering the pharmaceutical dosage forms.
1. A process for obtaining a first extract of Cannabis sativa, Cannabis indica, or combination thereof, enriched with at least one of: cannabinol; cannabinolic acid; Δ(9)-tetrahydrocannabinolic acid; Δ(9)-cannabidiol; Δ(9)-tetrahydrocannabidiolic acid; Δ(8)-tetrahydrocannabinolic acid; Δ(8)-tetrahydrocannabidiol; Δ(8)-tetrahydrocannabidiolic acid; Δ(9)-tetrahydrocannabivarin; cannabigerol; cannabigerolic acid; cannabichromene; cannabichromenic acid; cannabicyclol; and cannabicyclolic acid, and
a second extract of Cannabis sativa, Cannabis indica, or combination thereof, enriched with at least one of Δ(8)-tetrahydrocannabinol and Δ(9)-tetrahydrocannabinol, the process comprising:
(a) contacting Cannabis sativa, Cannabis indica, or a combination thereof, with carbon dioxide as the sole supercritical fluid solvent, at a pressure of 1,400 psi-3,800 psi, at a temperature of 35° C.-65° C., for a period of time of 1.5 hours to 8.5 hours, to provide an enriched extract of Cannabis sativa, Cannabis indica, or combination thereof; and
(b) removing the supercritical carbon dioxide from the extract; wherein the (a) contacting of the Cannabis sativa, Cannabis indica, or a combination thereof, with the supercritical carbon dioxide and then the (b) removing the supercritical carbon dioxide, is carried out two or more times, such that the process is a supercritical carbon dioxide fluid extraction;
wherein a first supercritical carbon dioxide fluid extraction is carried out such that:
(i) the contacting of the Cannabis sativa, Cannabis indica, or a combination thereof, with the supercritical carbon dioxide, is carried out at a pressure of 1,600 psi-2,000 psi, at a temperature of 35° C.-65° C., for a period of time of 1.5 hours-4.5 hours, to provide the first extract wherein a second supercritical carbon dioxide fluid extraction is carried out such that:
(ii) the contacting of the Cannabis sativa, Cannabis indica, or a combination thereof, with the supercritical carbon dioxide, is carried out at a pressure of 2,400 psi-3,600 psi, at a temperature of 35° C.-65° C., for a period of time of 3.5 hours-8.5 hours, to provide the second extract.
2. The process of claim 1 , wherein the first extract comprises no more than 5 wt. % in the aggregate Δ(8)-tetrahydrocannabinol and Δ(9)-tetrahydrocannabinol.
3. The process of claim 1 , wherein the first supercritical fluid extraction is carried out at a temperature of 44° C.-54° C.
4. The process of claim 1 , wherein the first supercritical fluid extraction is carried out for a period of time of 2 hours-4 hours.
5. The process of claim 1 , wherein the first extract is purified employing a technique selected from the group consisting of chromatography, adsorption, crystallization, distillation, liquid-liquid extraction, filtration, fractional distillation, precipitation, recrystallization, lyophilization, sublimation, and combinations thereof.
6. The process of claim 1 , wherein the first extract is purified employing a technique selected from the group consisting of chromatography, adsorption, crystallization, distillation, liquid-liquid extraction, filtration, fractional distillation, precipitation, recrystallization, lyophilization, sublimation, and combinations thereof, such that the first extract after the purification comprises at least 85 wt. % cannabinoids comprising at least one of cannabinolic acid; Δ(9)-tetrahydrocannabinolic acid; Δ(9)-cannabidiol; Δ(9)-tetrahydrocannabidiolic acid; Δ(8)-tetrahydrocannabinolic acid; Δ(8)-tetrahydrocannabidiol; Δ(8)-tetrahydrocannabidiolic acid; Δ(9)-tetrahydrocannabivarin; cannabigerol; cannabigerolic acid; cannabichromene; cannabichromenic acid; cannabicyclol; and cannabicyclolic acid.
7. The process of claim 1 , wherein the first extract is purified employing a technique selected from the group consisting of chromatography, adsorption, crystallization, distillation, liquid-liquid extraction, filtration, fractional distillation, precipitation, recrystallization, lyophilization, sublimation, and combinations thereof, such that the first extract after the purification comprises at least 98 wt. % cannabinoids comprising at least one of cannabinol; cannabinolic acid; Δ(9)-tetrahydrocannabinolic acid; Δ(9)-cannabidiol; Δ(9)-tetrahydrocannabidiolic acid; Δ(8)-tetrahydrocannabinolic acid; Δ(8)-tetrahydrocannabidiol; Δ(8)-tetrahydrocannabidiolic acid; Δ(9)-tetrahydrocannabivarin; cannabigerol; cannabigerolic acid; cannabichromene; cannabichromenic acid; cannabicyclol; and cannabicyclolic acid.
8. The process of claim 1 , wherein relative to the cannabis in step (a), the first extract includes a lower concentration of Δ(8)-tetrahydrocannabinol and Δ(9)-tetrahydrocannabinol.
9. The process of claim 1 , wherein the first extract comprises no more than 1 wt. % in the aggregate of Δ(8)-tetrahydrocannabinol and Δ(9)-tetrahydrocannabinol.
10. The process of claim 1 , wherein the second supercritical fluid extraction is carried out at a temperature of 44° C.-54° C.
11. The process of claim 1 , wherein the second supercritical fluid extraction is carried out for a period of time of 4-8 hours.
12. The process of claim 1 , wherein the second extract is purified employing a technique selected from the group consisting of chromatography, adsorption, crystallization, distillation, liquid-liquid extraction, filtration, fractional distillation, precipitation, recrystallization, lyophilization, sublimation, and combinations thereof.
13. The process of claim 2 , wherein the second extract is purified employing a technique selected from the group consisting of chromatography, adsorption, crystallization, distillation, liquid-liquid extraction, filtration, fractional distillation, precipitation, recrystallization, lyophilization, sublimation, and combinations thereof, such that the second extract enriched with Δ(8)-tetrahydrocannabinol and Δ(9)-tetrahydrocannabinol after the purification comprises at least 85 wt. % in the aggregate of Δ(8)-tetrahydrocannabinol and Δ(9)-tetrahydrocannabinol.
14. The process of claim 1 , wherein the second extract is purified employing a technique selected from the group consisting of chromatography, adsorption, crystallization, distillation, liquid-liquid extraction, filtration, fractional distillation, precipitation, recrystallization, lyophilization, sublimation, and combinations thereof, such that the second extract enriched with Δ(8)-tetrahydrocannabinol and Δ(9)-tetrahydrocannabinol after the purification comprises at least 95 wt. % in the aggregate of Δ(8)-tetrahydrocannabinol and Δ(9)-tetrahydrocannabinol.
15. The process of claim 1 , further comprising removing the supercritical fluid solvent from the second extract.
16. The process of claim 1 , wherein the second extract comprises at least about 65 wt. % in the aggregate of Δ(8)-tetrahydrocannabinol and Δ(9)-tetrahydrocannabinol.
17. The process of claim 1 , wherein relative to the cannabis in step (a), the second extract includes a lower concentration of cannabinoids comprising cannabinol; cannabinolic acid; Δ(9)-tetrahydrocannabinolic acid; Δ(9)-cannabidiol; Δ(9)-tetrahydrocannabidiolic acid; Δ(8)-tetrahydrocannabinolic acid; Δ(8)-tetrahydrocannabidiol; Δ(8)-tetrahydrocannabidiolic acid; Δ(9)-tetrahydrocannabivarin; cannabigerol; cannabigerolic acid; cannabichromene; cannabichromenic acid; cannabicyclol; cannabicyclolic acid; and combinations thereof.
18. The process of claim 1 , wherein relative to the cannabis in step (a), the second extract includes a lower concentration of cannabigerolic acid.
19. The process of claim 1 , wherein relative to the cannabis in step (a), the second extract includes a lower concentration of cannabinol.
20. The process of claim 1 , wherein relative to the cannabis in step (a), the second extract includes a lower concentration of Δ(9)-tetrahydrocannabinolic acid.
21. The process of claim 1 , wherein relative to the cannabis in step (a), the second extract includes a lower concentration of Δ(9)-cannabidiol.
22. The process of claim 1 , wherein relative to the cannabis in step (a), the second extract includes a lower concentration of Δ(9)-tetrahydrocannabidiolic acid.
23. The process of claim 1 , wherein the relative to the cannabis in step (a), the second extract includes a higher concentration of Δ(8)-tetrahydrocannabinol.
24. The process of claim 1 , wherein relative to the cannabis in step (a), the second extract includes a lower concentration of Δ(8)-tetrahydrocannabinolic acid.
25. The process of claim 1 , wherein relative to the cannabis in step (a), the second extract includes a higher concentration of Δ(8)-tetrahydrocannabinol and Δ(9)-tetrahydrocannabinol.
26. The process of claim 1 , wherein first extract comprises less than 10 wt. % in the aggregate of Δ(8)-tetrahydrocannabinol and Δ(9)-tetrahydrocannabinol.