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. Crystalline psilocybin characterized by X-ray powder diffraction (XRPD) peaks at 17.5±0.1 and 19.7±0.1° 2θ, wherein the crystalline psilocybin has a chemical purity of greater than 97% as determined by high-performance liquid chromatography (HPLC) analysis.
2. The crystalline psilocybin of claim 1 , further characterized by at least one XRPD peak at 11.5±0.1, 12.0±0.1, or 14.5±0.1° 2θ.
3. The crystalline psilocybin of claim 1 , further characterized by XRPD peaks at 11.5±0.1 and 12.0±0.1° 2θ.
4. The crystalline psilocybin of claim 1 , further characterized by XRPD peaks at 11.5±0.1 and 14.5±0.1° 2θ.
5. The crystalline psilocybin of claim 1 , further characterized by XRPD peaks at 12.0±0.1 and 14.5±0.1° 2θ.
6. The crystalline psilocybin of claim 2 , further characterized by at least one XRPD peak at 20.4±0.1, 22.2±0.1, 24.3±0.1, or 25.7±0.1° 2θ.
7. The crystalline psilocybin of claim 1 , having a chemical purity of greater than 98%.
8. The crystalline psilocybin of claim 1 , having a chemical purity of greater than 99%.
9. The crystalline psilocybin of claim 1 , comprising no single impurity greater than 1% as determined by HPLC analysis.
10. The crystalline psilocybin of claim 1 , having less than 1% psilocin as determined by HPLC analysis.
11. The crystalline psilocybin of claim 1 , having less than 0.5% psilocin as determined by HPLC analysis.
12. The crystalline psilocybin of claim 1 , further characterized by a water content of <0.5% w/w as determined by Karl Fisher Titration.
13. The crystalline psilocybin of claim 1 , having less than 1% phosphoric acid as determined by 31 P nuclear magnetic resonance ( 31 P NMR).
14. The crystalline psilocybin of claim 1 , having less than 0.5% phosphoric acid as determined by 31 P NMR.
15. The crystalline psilocybin of claim 1 , further characterized by a <0.5% w/w loss in the thermogravimetric analysis (TGA) thermogram between 25° C. and 200° C.
16. The crystalline psilocybin of claim 1 , further characterized by an endothermic event in a differential scanning calorimetry (DSC) thermogram having an onset temperature of between 205° C. and 220° C.
17. The crystalline psilocybin of claim 1 , further characterized by an endothermic event in a DSC thermogram having an onset temperature of between 145° C. and 155° C.
18. The crystalline psilocybin of claim 1 , comprising crystals with a size ranging from 50 to 200 microns.
19. A pharmaceutical composition comprising a psilocybin drug substance and a pharmaceutically acceptable excipient, wherein the drug substance comprises the crystalline psilocybin of claim 1 .
20. The pharmaceutical composition of claim 19 , wherein the pharmaceutical composition is a capsule.
21. The pharmaceutical composition of claim 19 , wherein the pharmaceutical composition is a tablet.
22. The pharmaceutical composition of claim 19 , comprising about 1 mg to about 40 mg of the psilocybin drug substance.
23. The pharmaceutical composition of claim 19 , comprising about 1 mg of the psilocybin drug substance.
24. The pharmaceutical composition of claim 19 , comprising about 25 mg of the psilocybin drug substance.
25. The pharmaceutical composition of claim 19 , wherein the psilocybin drug substance has a chemical purity of greater than 98%.
26. The pharmaceutical composition of claim 19 , wherein the psilocybin drug substance has a water content of <0.5% w/w as determined by Karl Fisher Titration.
27. The pharmaceutical composition of claim 19 , having less than 1% psilocin as determined by HPLC analysis.
28. The pharmaceutical composition of claim 19 , having less than 1% phosphoric acid as determined by 31 P NMR.