Solid forms of 2-[3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-methyl-4-[4-(oxetan-3-yl)piperazin-1-yl]pent-2-enenitrile
Solid forms of Compound (I): are disclosed. Pharmaceutical compositions comprising the same, methods of treating disorders and conditions mediated by BTK activity using the same, and methods for making Compound (I) and solid forms thereof are also disclosed.
1. A solid form of Compound (I):
wherein the solid form is characterized by a mean bulk density greater than 0.3 g/cc.
2. The solid form according to claim 1 , wherein the solid form is characterized by a mean tapped density between 0.7 g/cc and 0.9 g/cc.
3. The solid form according to claim 1 , wherein the solid form is characterized by a Hausner ratio less than or equal to 1.2.
4. The solid form according to claim 1 , wherein the solid form is characterized by a total level of residual solvents less than 1%.
5. The solid form according to claim 1 , wherein the solid form is characterized by any one of the following:
(i) a residual dichloromethane level less than 1500 ppm; or
(ii) a residual methanol level less than 3000 ppm; or
(iii) a residual heptane level less than 5000 ppm; or
(iv) a residual isopropyl acetate level less than 5000 ppm; or
(v) a residual dichloromethane level less than 1500 ppm, a residual methanol level less than 3000 ppm, a residual heptane level less than 5000 ppm, and a residual isopropyl acetate level less than 5000 ppm.
6. The solid form according to claim 1 , wherein the solid form is characterized by any one of the following:
(i) a mass loss of less than 5 wt. % between 20° C. and 240° C. by thermogravimetric analysis; or
(ii) a glass transition temperature (T g ) greater than 90° C. at 0% relative humidity; or
(iii) a mass loss of less than 5 wt. % between 20° C. and 240° C. by thermogravimetric analysis and a glass transition temperature (T g ) greater than 90° C. at 0% relative humidity.
7. The solid form according to claim 1 , wherein the solid form is characterized by any one of the following:
(i) a wet particle size distribution having a D 10 value greater than 70 μm; or
(ii) a wet particle size distribution having a D 50 value greater than 200 μm; or
(iii) a wet particle size distribution having a D 90 value greater than 400 μm; or
(iv) a wet particle size distribution having a D 10 value greater than 70 μm and a wet particle size distribution having a D 50 value greater than 200 μm; or
(v) a wet particle size distribution having a D 10 value greater than 70 μm, a wet particle size distribution having a D 50 value greater than 200 μm, and a wet particle size distribution having a D 90 value greater than 400 μm.
8. The solid form according to claim 1 , wherein the solid form is substantially amorphous.
9. A pharmaceutical composition comprising at least one pharmaceutically acceptable excipient and the solid form according to claim 1 .
10. A solid form of Compound (I):
wherein the solid form is characterized by a wet particle size distribution having a D 10 value less than 10 μm.
11. The solid form according to claim 10 , wherein the solid form is characterized by any one of the following:
(i) a mean bulk density less than 0.3 g/cc; or
(ii) a mean tapped less than 0.3 g/cc; or
(iii) a mean bulk density less than 0.3 g/cc and a mean tapped less than 0.3 g/cc.
12. The solid form according to claim 10 , wherein the solid form is characterized by a total level of residual solvents less than 1%.
13. The solid form according to claim 10 , wherein the solid form is characterized by any one of the following:
(i) a residual heptane level less than 500 ppm; or
(ii) a residual methanol level less than 500 ppm; or
(iii) a residual dichloromethane level less than 1500 ppm; or
(iv) a residual isopropyl acetate level less than 4000 ppm; or
(v) a residual heptane level less than 500 ppm, a residual methanol level less than 500 ppm, a residual dichloromethane level less than 1500 ppm, and a residual isopropyl acetate level less than 4000 ppm.
14. The solid form according to claim 10 , wherein the solid form is characterized by any one of the following:
(i) a mass loss of less than 5 wt. % between 20° C. and 240° C. by thermogravimetric analysis; or
(ii) a glass transition temperature (T g ) greater than 90° C. at 0% relative humidity; or
(iii) a mass loss of less than 5 wt. % between 20° C. and 240° C. by thermogravimetric analysis and a glass transition temperature (T g ) greater than 90° C. at 0% relative humidity.
15. The solid form according to claim 10 , wherein the solid form is characterized by any one of the following:
(i) a wet particle size distribution having a D 10 value between 1 μm and 2 μm; or
(ii) a wet particle size distribution having a D 10 value between 5 μm and 6 μm; or
(iii) a wet particle size distribution having a D 50 value less than 100 μm; or
(iv) a wet particle size distribution having a D 90 value less 200 μm; or
(v) a wet particle size distribution having a D 10 value between 1 μm and 2 μm, a wet particle size distribution having a D 10 value between 5 μm and 6 μm, a wet particle size distribution having a D 50 value less than 100 μm, and a wet particle size distribution having a D 90 value less 200 μm.
16. The solid form according to claim 10 , wherein the solid form is substantially amorphous.