Colchicine solid-state forms; methods of making; and methods of use thereof

1. A colchicine solid state form, comprising:

a. Colchicine Form B cyclohexane solvate comprising XRPD peak positions at 5.79, 10.50, 12.48, 14.73, 16.38, 17.47, 19.33, 19.78, 21.27, 22.57, 23.86, and 25.11±0.2 degrees 2-theta;

b. Colchicine Form D ethanol solvate comprising XRPD peak positions at 9.45, 10.88, 13.63, 16.26, 18.31, 18.76, 21.16, and 25.10±0.2 degrees 2-theta;

c. Colchicine Form G acetone solvate comprising XRPD peak positions at 9.39, 12.01, 12.41, 16.44, 18.87, 19.67, 20.94, 22.28, 23.82, and 25.59±0.2 degrees 2-theta;

d. Colchicine Form H dioxane solvate comprising XRPD peak positions at 12.04, 13.32, 14.57, 15.78, 17.04, 18.05, 18.25, 20.35, 20.59, 22.00, 23.64, 24.13, and 24.35±0.2 degrees 2-theta;

e. Colchicine Form I tetrahydrofuran solvate comprising XRPD peak positions at 5.84, 9.86, 10.64, 11.74, 14.77, 16.45, 17.61, 19.10, 19.96, 21.44, 23.94, 24.12, 24.47, and 25.10±0.2 degrees 2-theta;

f. Colchicine Form J toluene solvate comprising XRPD peak positions at 9.46, 10.43, 11.96, 13.27, 14.50, 15.67, 17.00, 18.10, 19.86, 20.43, 24.26, 25.62, 26.30, and 27.42±0.2 degrees 2-theta; or

g. Colchicine Form L mesitylene solvate comprising Raman peaks at 2935, 1591, 1570, 1553, 1503, 1432, 1349, 1323, and 1286±2 cm −1 .

2. The colchicine solid state form of claim 1 , wherein Colchicine Form B comprises one or more of the following:

XRPD peak positions at 5.79, 10.50, 12.48, 14.73, 16.38, 17.47, 19.33, 19.78, 21.27, 22.57, 23.86, and 25.11±0.2 degrees 2-theta;

XRPD peak positions as in Table 6;

an X-ray powder diffraction pattern as in FIG. 5 ;

Raman peaks at 2936, 1594, 1571, 1553, 1503, 1432, 1350, 1323, and 1286±2 cm −1 ;

Raman peaks as in Table 6; or

a Raman spectrum as in FIG. 4 .

3. The colchicine solid state form of claim 1 , wherein Colchicine Form D comprises one or more of the following:

XRPD peak positions at 9.45, 10.88, 13.63, 16.26, 18.31, 18.76, 21.16, and 25.10±0.2 degrees 2-theta;

XRPD peak positions as in Table 10;

an X-ray powder diffraction pattern as in FIG. 8 ;

Raman peaks at 2933, 1588, 1569, 1549, 1501, 1443, 1436, 1352, and 1325±2 cm − ;

Raman peaks as in Table 10;

a Raman spectrum as in FIG. 9 ; or

a melting peak of about 95° C. by DSC analysis.

4. The colchicine solid state form of claim 1 , wherein Colchicine Form G comprises one or more of the following:

XRPD peak positions at 9.39, 12.01, 12.41, 16.44, 18.87, 19.67, 20.94, 22.28, 23.82, and 25.59±0.2 degrees 2-theta;

XRPD peak positions as in Table 17;

an X-ray powder diffraction pattern as in FIG. 14 ;

Raman peaks at 2935, 1596, 1559, 1504, 1431, 1347, 1323, and 1292±2 cm −1 ;

Raman peaks as in Table 17;

a Raman spectrum as in FIG. 15 ; or

a melting peak of about 87° C. by DSC analysis.

5. The colchicine solid state form of claim 1 , wherein Colchicine Form H comprises one or more of the following:

XRPD peak positions at 12.04, 13.32, 14.57, 15.78, 17.04, 18.05, 18.25, 20.35, 20.59, 22.00, 23.64, 24.13, and 24.35±0.2 degrees 2-theta;

XRPD peak positions as in Table 19;

an X-ray powder diffraction pattern as in FIG. 16 ;

Raman peaks at 2940, 2846, 1573, 1503, 1442, 1430, 1353, 1324, and 1283±2 cm −1 ;

Raman peaks as in Table 19; or

a Raman spectrum as in FIG. 17 .

6. The colchicine solid state form of claim 1 , wherein Colchicine Form I comprises one or more of the following:

XRPD peak positions at 5.84, 9.86, 10.64, 11.74, 14.77, 16.45, 17.61, 19.10, 19.96, 21.44, 23.94, 24.12, 24.47, and 25.10±0.2 degrees 2-theta;

XRPD peak positions as in Table 21;

an X-ray powder diffraction pattern as in FIG. 18 ;

Raman peaks at 2939, 2840, 1594, 1569, 1553, 1503, 1433, 1350, 1323, and 1286±2 cm −1 ;

Raman peaks as in Table 21; or

a Raman spectrum as in FIG. 19 .

7. The colchicine solid state form of claim 1 , wherein Colchicine Form J comprises one or more of the following:

XRPD peak positions at 9.46, 10.43, 11.96, 13.27, 14.50, 15.67, 17.00, 18.10, 19.86, 20.43, 24.26, 25.62, 26.30, and 27.42±0.2 degrees 2-theta;

XRPD peak positions as in Table 23;

an X-ray powder diffraction pattern as in FIG. 20 ;

Raman peaks at 3065, 2933, 1590, 1574, 1502, 1441, 1430, 1350, 1321, and 1283±2 cm −1 ;

Raman peaks as in Table 23; or

a Raman spectrum as in FIG. 21 .

8. The colchicine solid state form of claim 1 , wherein Colchicine Form L comprises one or more of the following:

Raman peaks at 2935, 1591, 1570, 1553, 1503, 1432, 1349, 1323, and 1286±2 cm −1 ;

Raman peaks as in Table 27; or

a Raman spectrum as in FIG. 24 .

9. A composition comprising:

a colchicine solid state form, and

a pharmaceutically acceptable excipient;

wherein the colchicine solid state form comprises

a. Colchicine Form B cyclohexane solvate comprising XRPD peak positions at 5.79, 10.50, 12.48, 14.73, 16.38, 17.47, 19.33, 19.78, 21.27, 22.57, 23.86, and 25.11±0.2 degrees 2-theta;

b. Colchicine Form D ethanol solvate comprising XRPD peak positions at 9.45, 10.88, 13.63, 16.26, 18.31, 18.76, 21.16, and 25.10±0.2 degrees 2-theta;

c. Colchicine Form G acetone solvate comprising XRPD peak positions at 9.39, 12.01, 12.41, 16.44, 18.87, 19.67, 20.94, 22.28, 23.82, and 25.59±0.2 degrees 2-theta;

d. Colchicine Form H dioxane solvate comprising XRPD peak positions at 12.04, 13.32, 14.57, 15.78, 17.04, 18.05, 18.25, 20.35, 20.59, 22.00, 23.64, 24.13, and 24.35±0.2 degrees 2-theta;

e. Colchicine Form I tetrahydrofuran solvate comprising XRPD peak positions at 5.84, 9.86, 10.64, 11.74, 14.77, 16.45, 17.61, 19.10, 19.96, 21.44, 23.94, 24.12, 24.47, and 25.10±0.2 degrees 2-theta;

f. Colchicine Form J toluene solvate comprising XRPD peak positions at 9.46, 10.43, 11.96, 13.27, 14.50, 15.67, 17.00, 18.10, 19.86, 20.43, 24.26, 25.62, 26.30, and 27.42±0.2 degrees 2-theta; or

g. Colchicine Form L mesitylene solvate comprising Raman peaks at 2935, 1591, 1570, 1553, 1503, 1432, 1349, 1323, and 1286±2 cm −1 .

10. A method of preparing colchicine solid state Form D, G, H, I, or J of claim 1 , comprising:

suspending colchicine in a solvent system to form a slurry mixture; and

slurrying the slurry mixture until colchicine Form D, G, H, I, or J is formed,

wherein the solvent system comprises

ethanol or ethanol and cyclohexane in the process to prepare colchicine Form D;

acetone in the process to prepare colchicine Form G;

1,4-dioxane in the process to prepare colchicine Form H;

tetrahydrofuran in the process to prepare colchicine Form I; and

toluene or toluene and acetonitrile in the process to prepare colchicine Form J;

optionally further comprising seeding the slurry mixture; and

optionally further comprising sonicating the slurry mixture.

11. A method of preparing colchicine solid state Form B or D of claim 1 , comprising:

dissolving colchicine in a solvent system; and

adding an antisolvent to precipitate Form B or D,

wherein the solvent system to prepare Form B is cyclohexane and ethanol and the antisolvent is cyclohexane; and

wherein the solvent system to prepare Form D is n-octane and ethanol and the antisolvent is n-octane.

12. A method of preparing colchicine solid state Form E, comprising:

drying colchicine Form D under an inert atmosphere.

13. A method of preparing colchicine solid state Form L of claim 1 , comprising:

crystallizing colchicine from a mixture of colchicine and mesitylene.