Claims for Patent: 10,941,142

Summary for Patent: 10,941,142

Title:	Formulations of a compound modulating kinases
Abstract:	Provided are compositions comprising Compound I having the following structure: ##STR00001## or a pharmaceutically acceptable salt thereof, and a solubilizing agent; methods of making the same; and methods of using the same.
Inventor(s):	Ibrahim; Prabha N. (Mountain View, CA), Rezaei; Hamid (Berkeley, CA), Visor; Gary Conard (Castro Valley, CA), Kamo; Tomoari (Tokyo, JP), Yamakose; Hiroshi (Tokyo, JP)
Assignee:	Plexxikon Inc. (Berkeley, CA)
Application Number:	16/510,764
Patent Claims:	1. A method for preparing a composition comprising 40% to 60% W/W of Compound I: ##STR00005## wherein Compound I is a crystalline HCl salt characterized by an X-ray powder diffractogram comprising peaks (.+-.0.2.degree.) at 7.3, 23.3 and 28.2.degree.2.theta. as determined on a diffractometer using Cu-K.alpha. 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; wherein the method comprises (1) mixing Compound I and the poloxamer to provide a first mixture; (2) roller-compacting the first mixture to provide roller-compacted ribbons; (3) milling the roller-compacted ribbons to provide granules; (4) blending the granules, the excipient and the disintegrant to form a second mixture; and (5) blending the second mixture and the lubricant to provide a final blend. 2. The method of claim 1, wherein the mixing in (1) employs a convection mixer; the roller-compacting in (2) employs a dry granulator to provide roller-compacted ribbons; the milling in (3) employs screening mills or cutting mills; the blending in (4) employs a diffusion mixer; and the blending in (5) employs a diffusion mixer. 3. The method of claim 1, wherein the poloxamer is poloxamer 407. 4. The method of claim 1, wherein the excipient is mannitol; the disintegrant is crospovidone; and the lubricant is magnesium stearate. 5. The method of claim 1, wherein the poloxamer is poloxamer 407; the excipient is mannitol; the disintegrant is crospovidone; and the lubricant is magnesium stearate. 6. A composition prepared by the method of claim 1. 7. The composition of claim 6, wherein the poloxamer is poloxamer 407. 8. The composition of claim 6, wherein the diffractogram further comprises peaks at 16.6 and 20.9.degree.2.theta..+-.0.2.degree.. 9. The composition of claim 6, comprising 45% to 55% W/W of Compound I; 24% to 32% W/W of poloxamer; 14% to 20% W/W of excipient; 2% to 4% W/W of disintegrant; and 1.0% to 2.5% W/W of lubricant. 10. The composition of claim 6, comprising 48% to 53% W/W of Compound I; 26% to 29% W/W of poloxamer; 15% to 18% W/W of excipient; 2.5% to 3.5% W/W of disintegrant; and 1.2% to 1.8% W/W of lubricant. 11. The composition of claim 6, comprising about 51.2% W/W of Compound I; about 27.6% W/W of poloxamer; about 16.8% W/W of excipient; about 3% W/W of disintegrant; and about 1.5% W/W of lubricant. 12. The composition of claim 6, wherein the excipient is mannitol; the disintegrant is crospovidone; and the lubricant is magnesium stearate. 13. The composition of claim 6, wherein the poloxamer is poloxamer 407; the excipient is mannitol; the disintegrant is crospovidone; and the lubricant is magnesium stearate. 14. The composition of claim 13, 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. 15. The composition of claim 13, 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 of magnesium stearate. 16. The composition of claim 13, comprising about 51.2% W/W of Compound I; about 27.6% W/W of poloxamer 407; about 16.8% W/W of mannitol; about 3% W/W of crospovidone; and about 1.5% W/W of magnesium stearate.