Crystalline forms of compositions comprising psilocin and psilocybin
The present disclosure provides a composition comprising crystalline forms A, B, and C of psilocin and psilocybin. Solvent screen, X-ray powder diffractogram, thermogravimetric mass spectroscopy, differential scanning calorimetry, 1 H-NMR, dynamic vapor sorption, and UPLC data on each of the crystalline forms is presented, along with methods preparing each of the crystalline forms.
1. A composition comprising a crystalline form of psilocin and psilocybin:
wherein the crystalline form is crystalline Form A; and
wherein crystalline Form A is characterized by a XRPD patter comprising a peak at a 2θ angle of 10.1°, 19.16°, 14.54°, 16.5°, 13.44°, 23.42°, and 8.62.
2. The composition of claim 1 , wherein the XRPD pattern further comprises a peak at a 2θ angles of 10.74°, 25.3°, and 24.07°.
3. The composition of claim 1 , wherein crystalline Form A is characterized by a DSC plot comprising a sharp endothermic event at a temperature of about 255° C.
4. The composition of claim 1 , wherein crystalline Form A has ratio of psilocybin to psilocin of about 1:1.
5. The composition of claim 1 , wherein crystalline Form A has a chemical purity of about 95% or greater.
6. The composition of claim 1 , wherein crystalline Form A contains not more than about 5 mol % of other solid forms.
7. The composition of claim 1 , wherein crystalline Form A is a co-crystal formed between psilocin and psilocybin.
8. A pharmaceutical composition comprising a crystalline form of psilocin and psilocybin and a pharmaceutically acceptable excipient
wherein the crystalline form is crystalline Form A; and
wherein crystalline Form A is characterized by a XRPD patter comprising a peak at a 2θ angle of 10.1°, 19.16°, 14.54°, 16.5°, 13.44°, 23.42°, and 8.62.
9. The pharmaceutical composition of claim 8 , wherein the XRPD pattern further comprises a peak at a 2θ angles of 10.74°, 25.3°, and about 24.07°.
10. The pharmaceutical composition of claim 8 , wherein crystalline Form A has ratio of psilocybin to psilocin of about 1:1.
11. The pharmaceutical composition of claim 8 , wherein crystalline Form A has a chemical purity of about 95% or greater.
12. The pharmaceutical composition of claim 8 , wherein crystalline Form A is a co-crystal formed between psilocin and psilocybin.
13. A composition comprising a crystalline form of psilocin and psilocybin:
wherein the crystalline form is Form A,
wherein crystalline Form A is characterized by unit cell parameters which are substantially equal to the following:
Unit cell dimensions:
a=9.3674(3) Å
b=11.2660(6) Å
c=24.2741(9) Å
α=90 degrees
β=90 degrees
γ=90 degrees
Space group=P 2 1 2 1 2 1
Molecules/asymmetric unit=1.
14. The composition of claim 13 , wherein the unit cell parameters of crystalline Form A were measured about 296K.
15. The composition of claim 13 , wherein crystalline Form A has a geometry of hydrogen bonds substantially as listed in the table below:
D-H...A
D-H [Å]
H...A [Å]
D...A [Å]
D-H...A [°]
O1-H1...N23 i
0.88(2)
1.60(2)
2.46(2)
162(2)
N11-H11...O3 ii
0.96(5)
2.17(4)
2.97(4)
140(6)
N17-H17...O2 iii
0.85(7)
1.83(7)
2.59(6)
147(8)
N28-H28...O1 iv
0.87(7)
2.32(6)
3.13(5)
153(10)
O34-H34...O3 v
0.88(10)
1.69(8)
2.49(7)
151(5).
16. The composition of claim 13 , wherein crystalline Form A has atomic coordinates of non-hydrogen atoms substantially as listed in the table below:
x
y
z
U(eq)
O1
0.1251(14)
0.0326(16)
0.4198(4)
0.0253
O2
0.077(3)
0.0094(13)
0.3153(5)
0.0253
O3
0.190(3)
0.190(2)
0.3483(6)
0.0253
P4
0.0916(7)
0.0915(7)
0.3636(3)
0.0253
O5
−0.054(2)
0.157(3)
0.3724(5)
0.0253
C6
−0.1818(8)
0.102(5)
0.3771(8)
0.0253
C7
−0.221(2)
0.009(6)
0.4089(13)
0.0253
C8
−0.357(3)
−0.030(9)
0.4084(19)
0.0253
C9
−0.466(2)
0.022(11)
0.375(2)
0.0253
C10
−0.4261(9)
0.116(10)
0.3436(15)
0.0253
N11
−0.512(3)
0.188(12)
0.3068(16)
0.0253
C12
−0.386(5)
0.277(10)
0.2836(13)
0.0253
C13
−0.265(4)
0.250(7)
0.3069(10)
0.0253
C14
−0.2791(18)
0.156(7)
0.3445(10)
0.0253
C15
−0.139(6)
0.313(5)
0.2890(13)
0.0253
C16
−0.082(4)
0.261(6)
0.2343(10)
0.0253
N17
0.054(6)
0.324(5)
0.2219(15)
0.0253
C18
0.140(5)
0.246(6)
0.1809(13)
0.0253
C19
0.146(7)
0.370(3)
0.269(2)
0.0253
C21
0.8842(18)
0.5884(19)
0.9383(6)
0.0253
C22
0.7490(17)
0.7295(10)
0.9827(10)
0.0253
N23
0.8087(12)
0.6116(8)
0.9893(5)
0.0253
C24
0.7012(15)
0.5244(13)
1.0037(8)
0.0253
C25
0.591(2)
0.533(3)
0.9591(11)
0.0253
C26
0.508(4)
0.422(3)
0.9490(17)
0.0253
C27
0.543(5)
0.306(3)
0.963(2)
0.0253
N28
0.435(7)
0.236(4)
0.942(3)
0.0253
C29
0.337(7)
0.302(6)
0.917(3)
0.0253
C30
0.212(8)
0.268(7)
0.891(3)
0.0253
C31
0.124(7)
0.356(9)
0.868(3)
0.0253
C32
0.161(6)
0.474(8)
0.872(3)
0.0253
C33
0.292(5)
0.508(6)
0.899(3)
0.0253
O34
0.330(4)
0.628(6)
0.906(3)
0.0253
C35
0.379(5)
0.422(5)
0.920(2)
0.0253.
17. The composition of claim 13 , wherein crystalline Form A has atomic coordinates of hydrogen atoms substantially as listed in the table below:
x
y
z
U(eq)
H1
0.1396(11)
0.074(2)
0.4502(3)
0.0253
H7
−0.151(3)
−0.029(5)
0.4319(14)
0.0253
H8
−0.379(5)
−0.097(9)
0.431(2)
0.0253
H9
−0.563(3)
−0.005(13)
0.374(2)
0.0253
H11
−0.612(2)
0.172(14)
0.3030(19)
0.0253
H12
−0.389(6)
0.337(10)
0.2556(15)
0.0253
H15A
−0.075(5)
0.294(4)
0.3185(12)
0.0253
H15B
−0.147(8)
0.398(5)
0.2858(18)
0.0253
H16A
−0.146(5)
0.280(7)
0.2048(11)
0.0253
H16B
-0.074(3)
0.176(5)
0.2375(8)
0.0253
H17
0.041(8)
0.386(5)
0.2026(19)
0.0253
H18A
0.205(4)
0.181(6)
0.1844(12)
0.0253
H18B
0.203(6)
0.295(7)
0.1601(17)
0.0253
H18C
0.075(4)
0.206(7)
0.1563(10)
0.0253
H19A
0.213(7)
0.336(3)
0.2941(19)
0.0253
H19B
0.086(8)
0.405(2)
0.296(2)
0.0253
H19C
0.211(9)
0.429(4)
0.255(2)
0.0253
H21A
0.951(2)
0.627(3)
0.9141(7)
0.0253
H21B
0.817(3)
0.575(3)
0.9093(5)
0.0253
H21C
0.944(2)
0.520(2)
0.9427(10)
0.0253
H22A
0.778(2)
0.8072(10)
0.9708(14)
0.0253
H22B
0.715(2)
0.7579(14)
1.0176(12)
0.0253
H22C
0.6710(17)
0.7266(16)
0.9571(11)
0.0253
H24A
0.6599(17)
0.542(2)
1.0390(8)
0.0253
H24B
0.742(2)
0.4463(11)
1.0054(11)
0.0253
H25A
0.635(3)
0.565(3)
0.9267(9)
0.0253
H25B
0.5179(14)
0.587(3)
0.9706(16)
0.0253
H27
0.629(5)
0.2905(18)
0.984(3)
0.0253
H28
0.436(8)
0.159(4)
0.946(4)
0.0253
H30
0.186(9)
0.185(8)
0.890(4)
0.0253
H31
0.037(8)
0.334(10)
0.851(4)
0.0253
H32
0.100(6)
0.533(9)
0.856(4)
0.0253
H34
0.294(4)
0.682(7)
0.884(3)
0.0253.
18. A pharmaceutical composition comprising a crystalline form of psilocin and psilocybin and a pharmaceutically acceptable excipient
wherein the crystalline form is crystalline Form A; and
wherein crystalline Form A is characterized by unit cell parameters which are substantially equal to the following:
Unit cell dimensions:
a=9.3674(3) Å
b=11.2660(6) Å
c=24.2741(9) Å
α=90 degrees
β=90 degrees
γ=90 degrees
Space group=P 2 1 2 1 2 1
Molecules/asymmetric unit=1.
19. The pharmaceutical composition of claim 18 , wherein the unit cell parameters of crystalline Form A were measured about 296K.
20. The pharmaceutical composition of claim 18 , wherein crystalline Form A has a geometry of hydrogen bonds substantially as listed in the table below:
D-H...A
D-H [Å]
H...A [Å]
D...A [Å]
D-H...A [°]
O1-H1...N23 i
0.88(2)
1.60(2)
2.46(2)
162(2)
N11-H11...O3 ii
0.96(5)
2.17(4)
2.97(4)
140(6)
N17-H17...O2 iii
0.85(7)
1.83(7)
2.59(6)
147(8)
N28-H28...O1 iv
0.87(7)
2.32(6)
3.13(5)
153(10)
O34-H34...O3 v
0.88(10)
1.69(8)
2.49(7)
151(5).
21. The pharmaceutical composition of claim 18 , wherein crystalline Form A has atomic coordinates of non-hydrogen atoms substantially as listed in the table below:
x
y
z
U(eq)
O1
0.1251(14)
0.0326(16)
0.4198(4)
0.0253
O2
0.077(3)
0.0094(13)
0.3153(5)
0.0253
O3
0.190(3)
0.190(2)
0.3483(6)
0.0253
P4
0.0916(7)
0.0915(7)
0.3636(3)
0.0253
O5
−0.054(2)
0.157(3)
0.3724(5)
0.0253
C6
−0.1818(8)
0.102(5)
0.3771(8)
0.0253
C7
−0.221(2)
0.009(6)
0.4089(13)
0.0253
C8
−0.357(3)
−0.030(9)
0.4084(19)
0.0253
C9
−0.466(2)
0.022(11)
0.375(2)
0.0253
C10
−0.4261(9)
0.116(10)
0.3436(15)
0.0253
N11
−0.512(3)
0.188(12)
0.3068(16)
0.0253
C12
−0.386(5)
0.277(10)
0.2836(13)
0.0253
C13
−0.265(4)
0.250(7)
0.3069(10)
0.0253
C14
−0.2791(18)
0.156(7)
0.3445(10)
0.0253
C15
−0.139(6)
0.313(5)
0.2890(13)
0.0253
C16
−0.082(4)
0.261(6)
0.2343(10)
0.0253
N17
0.054(6)
0.324(5)
0.2219(15)
0.0253
C18
0.140(5)
0.246(6)
0.1809(13)
0.0253
C19
0.146(7)
0.370(3)
0.269(2)
0.0253
C21
0.8842(18)
0.5884(19)
0.9383(6)
0.0253
C22
0.7490(17)
0.7295(10)
0.9827(10)
0.0253
N23
0.8087(12)
0.6116(8)
0.9893(5)
0.0253
C24
0.7012(15)
0.5244(13)
1.0037(8)
0.0253
C25
0.591(2)
0.533(3)
0.9591(11)
0.0253
C26
0.508(4)
0.422(3)
0.9490(17)
0.0253
C27
0.543(5)
0.306(3)
0.963(2)
0.0253
N28
0.435(7)
0.236(4)
0.942(3)
0.0253
C29
0.337(7)
0.302(6)
0.917(3)
0.0253
C30
0.212(8)
0.268(7)
0.891(3)
0.0253
C31
0.124(7)
0.356(9)
0.868(3)
0.0253
C32
0.161(6)
0.474(8)
0.872(3)
0.0253
C33
0.292(5)
0.508(6)
0.899(3)
0.0253
O34
0.330(4)
0.628(6)
0.906(3)
0.0253
C35
0.379(5)
0.422(5)
0.920(2)
0.0253.
22. The pharmaceutical composition of claim 18 , wherein crystalline Form A has atomic coordinates of hydrogen atoms substantially as listed in the table below:
x
y
z
U(eq)
H1
0.1396(11)
0.074(2)
0.4502(3)
0.0253
H7
−0.151(3)
−0.029(5)
0.4319(14)
0.0253
H8
−0.379(5)
−0.097(9)
0.431(2)
0.0253
H9
−0.563(3)
−0.005(13)
0.374(2)
0.0253
H11
−0.612(2)
0.172(14)
0.3030(19)
0.0253
H12
−0.389(6)
0.337(10)
0.2556(15)
0.0253
H15A
−0.075(5)
0.294(4)
0.3185(12)
0.0253
H15B
−0.147(8)
0.398(5)
0.2858(18)
0.0253
H16A
−0.146(5)
0.280(7)
0.2048(11)
0.0253
H16B
-0.074(3)
0.176(5)
0.2375(8)
0.0253
H17
0.041(8)
0.386(5)
0.2026(19)
0.0253
H18A
0.205(4)
0.181(6)
0.1844(12)
0.0253
H18B
0.203(6)
0.295(7)
0.1601(17)
0.0253
H18C
0.075(4)
0.206(7)
0.1563(10)
0.0253
H19A
0.213(7)
0.336(3)
0.2941(19)
0.0253
H19B
0.086(8)
0.405(2)
0.296(2)
0.0253
H19C
0.211(9)
0.429(4)
0.255(2)
0.0253
H21A
0.951(2)
0.627(3)
0.9141(7)
0.0253
H21B
0.817(3)
0.575(3)
0.9093(5)
0.0253
H21C
0.944(2)
0.520(2)
0.9427(10)
0.0253
H22A
0.778(2)
0.8072(10)
0.9708(14)
0.0253
H22B
0.715(2)
0.7579(14)
1.0176(12)
0.0253
H22C
0.6710(17)
0.7266(16)
0.9571(11)
0.0253
H24A
0.6599(17)
0.542(2)
1.0390(8)
0.0253
H24B
0.742(2)
0.4463(11)
1.0054(11)
0.0253
H25A
0.635(3)
0.565(3)
0.9267(9)
0.0253
H25B
0.5179(14)
0.587(3)
0.9706(16)
0.0253
H27
0.629(5)
0.2905(18)
0.984(3)
0.0253
H28
0.436(8)
0.159(4)
0.946(4)
0.0253
H30
0.186(9)
0.185(8)
0.890(4)
0.0253
H31
0.037(8)
0.334(10)
0.851(4)
0.0253
H32
0.100(6)
0.533(9)
0.856(4)
0.0253
H34
0.294(4)
0.682(7)
0.884(3)
0.0253.