Formulations of a compound modulating kinases
Provided are compositions comprising Compound I having the following structure: or a pharmaceutically acceptable salt thereof, and a solubilizing agent; methods of making the same; and methods of using the same.
1. A composition comprising: 40% to 60% W/W of Compound I having the following structure:
and wherein Compound I is a crystalline HCl salt characterized by an X-ray powder diffractogram comprising peaks (±0.2°) at 7.3, 23.3 and 28.2° 2θ as determined on a diffractometer using Cu-Kα radiation; 20% to 35% W/W of a poloxamer; 10% to 22% W/W of an excipient; 1% to 5% W/W of a disintegrant; and 0.5% to 3% W/W of a lubricant.
2. The composition of claim 1 , wherein the poloxamer is poloxamer 407.
3. The composition of claim 1 , wherein the diffractogram further comprises peaks at 16.6 and 20.9° 2θ±0.2°.
4. The composition of claim 1 , wherein Compound I is characterized by:
i) a diffractogram substantially as shown in FIG. 1 ;
ii) a differential scanning calorimetry (DSC) thermogram comprising an endotherm at 234° C.;
iii) a DSC thermogram substantially as shown in FIG. 2 ;
iv) thermogravimetric analysis (TGA) comprising a thermogram substantially as shown in FIG. 3 ; or
v) a dynamic vapor sorption (DVS) curve substantially as shown in FIG. 4 .
5. The composition of claim 1 , comprising 45% to 55% W/W of Compound I; 24% to 32% W/W of the poloxamer; 14% to 20% W/W of the excipient; 2% to 4% W/W of the disintegrant; and 1.0% to 2.5% W/W of the lubricant.
6. The composition of claim 1 , comprising 48% to 53% W/W of Compound I; 26% to 29% W/W of the poloxamer; 15% to 18% W/W of the excipient; 2.5% to 3.5% W/W of the disintegrant; and 1.2% to 1.8% W/W of the lubricant.
7. The composition of claim 1 , comprising 51.2% (±3%) W/W of Compound I; 27.6% (±3%) W/W of the poloxamer; 16.8% (±3%) W/W of the excipient; 3% (±1%) W/W of the disintegrant; and 1.5% (±1%) W/W of the lubricant.
8. The composition of claim 1 , wherein the excipient is mannitol; the disintegrant is crospovidone; and the lubricant is magnesium stearate.
9. The composition of claim 8 , wherein the crospovidone is Polyplasdone® Ultra or Polyplasdone® Ultra-10.
10. The composition of claim 1 , wherein the poloxamer is poloxamer 407; the excipient is mannitol; the disintegrant is crospovidone; and the lubricant is magnesium stearate.
11. The composition of claim 10 , comprising 45% to 55% W/W of Compound I; 24% to 32% W/W of poloxamer 407; 14% to 20% W/W of mannitol; 2% to 4% W/W of crospovidone; and 1.0% to 2.5% W/W of magnesium stearate.
12. The composition of claim 10 , comprising 48% to 53% W/W of Compound I; 26% to 29% W/W of poloxamer 407; 15% to 18% W/W of mannitol; 2.5% to 3.5% W/W of crospovidone; and 1.2% to 1.8% W/W magnesium stearate.
13. The composition of claim 10 , comprising 51.2% W/W (±3%) of Compound I; 27.6% W/W (±3%) of poloxamer 407; 16.8% (±3%) W/W of mannitol; 3% W/W (±1%) of crospovidone; and 1.5% (±1%) W/W of magnesium stearate.
14. The composition of claim 10 , wherein the crospovidone is Polyplasdone® Ultra or Polyplasdone® Ultra-10.
15. The composition of claim 1 , wherein the composition is in a capsule form suitable for oral dosage.
16. The composition of claim 15 , wherein the capsule comprises hard gelatin or hypromellose.
17. The composition of claim 16 , wherein the capsule comprises hypromellose.
18. A method for preparing the composition of claim 1 comprising mixing Compound I, and a poloxamer in a convection mixer.
19. The method of claim 18 , wherein the convection mixer is a vertical high intensity mixer.
20. A composition prepared by the method of claim 18 .