Colchicine solid complex; methods of making; and methods of use thereof
View Patent ↗Disclosed are new colchicine solid complexes, methods of making the solid complexes as well as formulations prepared therefrom and uses thereof.
1. A solid complex, comprising:
colchicine and malic acid,
wherein the solid complex comprising colchicine and malic acid comprises a colchicine malic acid co-crystal exhibiting XRPD pattern comprising peak positions at 7.2, 11.1, 13.1, 16.3, 16.7, and 18.4±0.2 degrees 2-theta.
2. The solid complex of claim 1 , wherein the XRPD pattern further comprises peak positions at 6.0, 8.5, 19.9, 22.0, and 24.6±0.2 degrees 2-theta.
3. The solid complex of claim 1 , wherein the solid complex exhibits
FT-Raman pattern comprising peaks at 2935, 1595, 1500, 1444, 1350, 1324, and 1287±4 cm −1 ;
an endotherm peak of about 70° C. by differential scanning calorimetry analysis; or both.
4. The solid complex of claim 1 , wherein the solid complex has a ratio of about 1:1 malic acid:colchicine.
5. A solid complex, comprising:
colchicine and oxalic acid,
wherein the solid complex comprising colchicine and oxalic acid comprises a colchicine oxalic acid co-crystal exhibiting XRPD pattern comprising peak positions at 7.4, 9.2, 12.3, 14.4, 17.8, and 20.5±0.2 degrees 2-theta.
6. The solid complex of claim 5 , wherein the XRPD pattern further comprises peak positions at 9.4, 10.8, 12.0, 15.9, 18.9, and 23.7±0.2 degrees 2-theta.
7. The solid complex of claim 5 , wherein the solid complex exhibits
FT-Raman pattern comprising peaks at 2934, 1592, 1549, 1505, 1436, and 1401±4 cm −1 ;
an endotherm peak of about 144° C. by differential scanning calorimetry analysis; or both.
8. The solid complex of claim 5 , wherein the solid complex has a ratio of about 1:2 oxalic acid:colchicine.
9. A solid complex, comprising:
colchicine and para-toluenesulfonic acid,
wherein the solid complex comprising colchicine and para-toluenesulfonic acid comprises a colchicine para-toluenesulfonic acid co-crystal exhibiting XRPD pattern comprising peak positions at 6.6, 6.8, 12.8, 14.3, 15.1, 17.1, and 18.6±0.2 degrees 2-theta.
10. The solid complex of claim 9 , wherein the XRPD pattern further comprises peak positions at 9.6 and 22.7±0.2 degrees 2-theta.
11. The solid complex of claim 9 , wherein the solid complex exhibits
FT-Raman pattern comprising peaks at 1516, 1468, and 1322±4 cm −1 ;
an endotherm peak of about 198° C. by differential scanning calorimetry analysis; or both.
12. The solid complex of claim 9 , wherein the solid complex has a ratio of about 1:1 para-toluenesulfonic acid:colchicine.
13. A composition, comprising:
the solid complex according to claim 1 ; and
a pharmaceutically acceptable excipient.
14. The composition of claim 13 , wherein the composition is a solid oral dosage formulation.
15. A composition, comprising:
the solid complex according to claim 5 ; and
a pharmaceutically acceptable excipient.
16. The composition of claim 15 , wherein the composition is a solid oral dosage formulation.
17. A composition, comprising:
the solid complex according to claim 9 ; and
a pharmaceutically acceptable excipient.
18. The composition of claim 17 , wherein the composition is a solid oral dosage formulation.