Preparation of psilocybin, different polymorphic forms, intermediates, formulations and their use
This invention relates to the large-scale production of psilocybin for use in medicine. More particularly, it relates to a method of obtaining high purity crystalline psilocybin, particularly, in the form of Polymorph A. It further relates to a method for the manufacture of psilocybin and intermediates in the production thereof and formulations containing psilocybin.
1. A method of treating treatment resistant depression, the method comprising orally administering a therapeutically effective amount of an oral dosage form to a patient in need thereof, wherein the oral dosage form comprises:
a crystalline Polymorph A of psilocybin characterized by XRPD peaks at 11.5±0.1, 12.0±0.1, 14.5±0.1, 17.5±0.1 and 19.7±0.1°2θ, wherein the psilocybin has a chemical purity of greater than 97% as determined by HPLC analysis and
a pharmaceutically acceptable excipient.
2. The method of claim 1 , wherein about 1 mg to about 40 mg of the crystalline Polymorph A of psilocybin is administered.
3. The method of claim 1 , wherein about 10 mg to about 30 mg of the crystalline Polymorph A of psilocybin is administered.
4. The method of claim 1 , wherein about 1 mg of the crystalline Polymorph A of psilocybin is administered.
5. The method of claim 1 , wherein about 5 mg of the crystalline Polymorph A of psilocybin is administered.
6. The method of claim 1 , wherein about 10 mg of the crystalline Polymorph A of psilocybin is administered.
7. The method of claim 1 , wherein about 25 mg of the crystalline Polymorph A of psilocybin is administered.
8. The method of claim 1 , wherein the oral dosage form is a capsule.
9. The method of claim 1 , wherein the oral dosage form is a tablet.
10. The method of claim 1 , wherein the Polymorph A is further characterized by at least one peak selected from the group consisting of 20.4±0.1, 22.2±0.1, 24.3±0.1, and 25.7±0.1°2θ.
11. The method of claim 1 , wherein the psilocybin has no single impurity of greater than 1% as determined by HPLC analysis.
12. The method of claim 1 , wherein the patient is an adult.
13. A method of treating treatment resistant depression, the method comprising administering a therapeutically effective amount of psilocybin to a patient in need thereof,
wherein the psilocybin comprises a crystalline Polymorph A of psilocybin characterized by X-ray powder diffraction (XRPD) peaks at 11.5±0.1, 12.0±0.1, 14.5±0.1, 17.5±0.1 and 19.7±0.1°2θ, and
wherein the psilocybin has a chemical purity of greater than 97% as determined by HPLC analysis.
14. The method of claim 13 , wherein about 1 mg to about 40 mg of psilocybin is administered.
15. The method of claim 13 , wherein about 10 mg to about 30 mg of psilocybin is administered.
16. The method of claim 13 , wherein about 1 mg of psilocybin is administered.
17. The method of claim 13 , wherein about 5 mg of psilocybin is administered.
18. The method of claim 13 , wherein about 10 mg of psilocybin is administered.
19. The method of claim 13 , wherein about 25 mg of psilocybin is administered.
20. The method of claim 13 , wherein the psilocybin is orally administered.
21. The method of claim 13 , wherein the psilocybin is administered in a capsule.
22. The method of claim 13 , wherein the psilocybin is administered in a tablet.
23. The method of claim 13 , wherein the Polymorph A is further characterized by at least one peak selected from the group consisting of 20.4±0.1, 22.2±0.1, 24.3±0.1, and 25.7±0.1°2θ.
24. The method of claim 13 , wherein the psilocybin has no single impurity of greater than 1% as determined by HPLC analysis.
25. The method of claim 13 , wherein the patient is an adult.