Claims for Patent: 12,447,149

Summary for Patent: 12,447,149

Title:	Formulations of vimseltinib
Abstract:	Described herein, in part, are pharmaceutically acceptable formulations comprising a compound represented by Formula (I) and methods of preparing and using the formulations:
Inventor(s):	Ehab Hamed
Assignee:	Deciphera Pharmaceuticals LLC
Application Number:	US19/079,070
Patent Claims:	1. A pharmaceutically acceptable uniform oral dosage form comprising: a crystalline dihydrate form of a compound of Formula (I): wherein the crystalline dihydrate form is present in the oral dosage form in an amount selected from the group consisting of about 15.2 mg, about 21.7 mg, and about 32.5 mg; about 70% by weight to about 90% by weight lactose monohydrate based on the total weight of the oral dosage form; about 1% by weight to about 10% by weight cross-linked polyvinylpyrrolidone based on the total weight of the uniform oral dosage form; and about 0.1% by weight to about 3% by weight of one or more lubricants based on the total weight of the oral dosage form; wherein the uniform oral dosage form has an acceptance value of less than about 15 as determined by United States Pharmacopeia (USP) Uniformity of Dosage Unit <905>, wherein the crystalline dihydrate form of the compound of Formula (I) has an X-ray powder diffraction (XRPD) pattern comprising peaks, in terms of 2-theta, at about 10.9°, 16.8°, and 27.1° as measured by CuKa radiation. 2. The pharmaceutically acceptable uniform oral dosage form of claim 1, where in wherein the uniform oral dosage form has not more than about 10 mol % of a crystalline form of the compound of Formula (I) not having a diffraction pattern comprising peaks in terms of 2-theta, at about 10.9°, 16.8°, and 27.1° as measured by CuKa radiation. 3. The pharmaceutically acceptable uniform oral dosage form of claim 1, where in wherein the uniform oral dosage form has not more than about 5 mol % of a crystalline form of the compound of Formula (I) not having a diffraction pattern comprising peaks in terms of 2-theta, at about 10.9°, 16.8°, and 27.1° as measured by CuKa radiation. 4. The pharmaceutically acceptable uniform oral dosage form of claim 1, where in wherein the uniform oral dosage form has not more than about 3 mol % of a crystalline form of the compound of Formula (I) not having a diffraction pattern comprising peaks in terms of 2-theta, at about 10.9°, 16.8°, and 27.1° as measured by CuKa radiation. 5. The pharmaceutically acceptable uniform oral dosage form of claim 1, where in wherein the uniform oral dosage form has not more than about 1 mol % of a crystalline form of the compound of Formula (I) not having a diffraction pattern comprising peaks in terms of 2-theta, at about 10.9°, 16.8°, and 27.1° as measured by CuKa radiation. 6. The pharmaceutically acceptable uniform oral dosage form of claim 1, wherein the crystalline dihydrate form of the compound of Formula (I) has having an XRPD pattern substantially as shown in FIG. 1 . 7. The pharmaceutically acceptable uniform oral dosage form of claim 1, wherein the crystalline dihydrate form of the compound of Formula (I) has having a differential scanning calorimetry (DSC) thermogram comprising an endothermic event with onset between about 75° C. to about 95° C., an exothermic event with onset between about 123° C. to about 150° C., and an endothermic peak at about 215° C. 8. The pharmaceutically acceptable uniform oral dosage form of claim 1, wherein the crystalline dihydrate form of the compound of Formula (I) has having a differential scanning calorimetry (DSC) thermogram substantially as shown in FIG. 2 . 9. The pharmaceutically acceptable uniform oral dosage form of claim 1, wherein the crystalline dihydrate form of the compound of Formula (I) has having a thermogravimetric analysis (TGA) thermogram substantially as shown in FIG. 10. The pharmaceutically acceptable uniform oral dosage form of claim 1, wherein the crystalline dihydrate form of the compound of Formula (I) has an X-ray powder diffraction XRPD pattern comprising peaks, in terms of 2-theta, at about 5.9°, 10.9°, 11.9°, 13.7°, 16.8°, and 27.1° as measured by CuKa radiation. 11. A pharmaceutically acceptable capsule encapsulating a uniform pharmaceutical composition comprising: a solid-state dihydrate form of a compound represented by Formula (I): wherein the solid-state dihydrate form of the compound of Formula (I) is present in the capsule in an amount to provide about 2 mg, about 10 mg, about 14 mg, about 20 mg or about 30 mg of the free base of the compound; a means for making the composition uniform with an acceptance value of less than 15 according to USP <905>; and one or more pharmaceutically acceptable excipients, wherein the solid-state dihydrate form of the compound represented by Formula (I) has an X-ray powder diffraction (XRPD) pattern comprising peaks, in terms of 2-theta, at about 10.9°, 16.8°, and 27.1° as measured by CuKa radiation. 12. The pharmaceutically acceptable capsule of claim 11, wherein the one or more pharmaceutically acceptable excipients comprises: about 1% by weight to about 20% by weight of one or more disintegrants based on the weight of the uniform pharmaceutical composition; and about 0.1% by weight to about 10% by weight of one or more lubricants based on the weight of the pharmaceutically acceptable unit formulation uniform pharmaceutical composition. 13. The pharmaceutically acceptable capsule of claim 11, wherein the one or more pharmaceutically acceptable excipients comprises: about 1% by weight to about 10% by weight of one or more disintegrants based on the weight of the uniform pharmaceutical composition; and about 0.1% by weight to about 3% by weight of one or more lubricants based on the weight of the pharmaceutically acceptable unit formulation uniform pharmaceutical composition. 14. The pharmaceutically acceptable capsule of claim 11, where in the one or more pharmaceutically acceptable excipients includes about 1% by weight to about 10% by weight cross-linked polyvinylpyrrolidone based on the weight of the uniform pharmaceutical composition. 15. The pharmaceutically acceptable capsule of claim 11, wherein the solid-state dihydrate form of the compound of Formula (I) has an X-ray powder diffraction XRPD pattern comprising peaks, in terms of 2-theta, at about 5.9°, 10.9°, 11.9°, 13.7°, 16.8°, and 27.1° as measured by CuKa radiation. 16. The pharmaceutically acceptable capsule of claim 11, wherein the solid-state dihydrate form of the compound of Formula (I) has having an XRPD pattern substantially as shown in FIG. 1 . 17. An oral dosage form comprising a compound of Formula (I): wherein the compound is present in the oral dosage form as a free base, or a pharmaceutically acceptable salt of the compound and wherein the free base or pharmaceutically acceptable salt is in a crystalline dihydrate hydrate form; wherein the compound crystalline dihydrate form is present in the oral dosage form in an amount to provide about 2 mg, about 10 mg, about 14 mg, about 20 mg or about 30 mg of the free base of the compound; about 80% by weight to about 90% by weight of a filler based on the total weight of the oral dosage form, wherein the filler is selected from the group consisting of anhydrous lactose, lactose monohydrate, and lactose dihydrate; about 1% by weight to about 10% by weight cross-linked polyvinylpyrrolidone based on the total weight of the uniform oral dosage form; and about 0.1% by weight to about 3% by weight by weight of one or more lubricants based on the total weight of the oral dosage form, wherein the one or more lubricants are selected from the group consisting of sodium lauryl sulfate, magnesium stearate, aluminum stearate, calcium stearate, sodium stearyl fumarate, stearic acid and magnesium lauryl stearate, wherein the crystalline dihydrate form of the compound of Formula (I) has an X-ray powder diffraction pattern (XRPD) pattern comprising peaks, in terms of 2-theta, at about 10.9°, 16.8°, and 27.1° as measured by CuKa radiation. 18. The oral dosage form of claim 17, wherein greater than 90% of the compound of Formula (I) is released in 30 minutes, as determined by USP <711>, Apparatus 2 (paddles). 19. The oral dosage form of claim 17, wherein the one or more lubricants is magnesium stearate. 20. The oral dosage form of claim 17, wherein the filler is lactose monohydrate. 21. The oral dosage form of claim 17, wherein the crystalline dihydrate form of the compound of Formula (I) has an XRPD pattern comprising peaks, in terms of 2-theta, at about 5.9°, 10.9°, 11.9°, 13.7°, 16.8°, and 27.1° as measured by CuKa radiation. 22. The oral dosage form of claim 17, wherein the crystalline dihydrate form of the compound of Formula (I) has an XRPD pattern substantially as shown in FIG. 1 .