Amorphous solid dispersions of dasatinib and uses thereof

1. A method of treating a proliferative disorder in a patient in need thereof, the method comprising:

(a) administering to the patient a pharmaceutical composition comprising an amorphous solid dispersion, the amorphous solid dispersion consisting essentially of dasatinib, a methacrylic acid and ethyl acrylate copolymer that exhibits pH-dependent solubility, and optionally one or more functional components selected from the group consisting of antioxidants, wetting agents, and solubilizers; and

(b) co-administering to the patient a gastric acid-reducing agent;

wherein the dasatinib and the copolymer are present in the amorphous solid dispersion in a w/w ratio of 30:70 to 95:5 (dasatinib:copolymer).

2. The method of claim 1 , wherein the gastric acid-reducing agent is administered to the patient shortly before the pharmaceutical composition is administered.

3. The method of claim 1 , wherein the gastric acid-reducing agent is administered to the patient concurrently with the administration of the pharmaceutical composition.

4. The method of claim 1 , wherein the gastric acid-reducing agent is administered to the patient shortly after the pharmaceutical composition is administered.

5. The method of claim 1 , wherein the amorphous solid dispersion includes one or more functional components selected from the group consisting of antioxidants, wetting agents, and solubilizers.

6. The method of claim 1 , wherein the amorphous solid dispersion consists of dasatinib and the copolymer.

7. A treatment regimen for treating a proliferative disorder in a patient in need thereof, the regimen comprising:

(a) administering to the patient a first dose, the first dose comprising a standard dosage of a proton pump inhibitor or an H 2 antagonist; and

(b) within 12 hours after the first dose, administering a second dose to the patient, the second dose comprising a therapeutically effective amount of a pharmaceutical composition comprising an amorphous solid dispersion, the amorphous solid dispersion consisting essentially of dasatinib, a methacrylic acid and ethyl acrylate copolymer that exhibits pH-dependent solubility, and optionally one or more functional components selected from the group consisting of antioxidants, wetting agents, and solubilizers;

wherein the dasatinib and the copolymer are present in the amorphous solid dispersion in a w/w ratio of 30:70 to 95:5 (dasatinib:copolymer); and

wherein the therapeutically effective amount comprises 20 mg to 140 mg dasatinib.

8. The treatment regimen of claim 7 , wherein the first dose comprises a standard dosage of a proton pump inhibitor.

9. The treatment regimen of claim 7 , wherein the first dose comprises a standard dosage of a proton pump inhibitor selected from rabeprazole, esomeprazole, lansoprazole, omeprazole, pantoprazole, dexlansoprazole, or a combination thereof.

10. The treatment regimen of claim 7 , wherein the first dose comprises a standard dosage of an H 2 antagonist.

11. The treatment regimen of claim 7 , wherein the first dose comprises a standard dosage of an H 2 antagonist selected from famotidine, cimetidine, nizatidine, ranitidine, or a combination thereof.

12. The treatment regimen of claim 7 , wherein the second dose is administered within 8 hours after the first dose.

13. The treatment regimen of claim 7 , wherein the second dose is administered within 6 hours after the first dose.

14. The treatment regimen of claim 7 , wherein the second dose is administered within 4 hours after the first dose.

15. The treatment regimen of claim 7 , wherein the amorphous solid dispersion includes one or more functional components selected from the group consisting of antioxidants, wetting agents, and solubilizers.

16. The treatment regimen of claim 7 , wherein the amorphous solid dispersion consists of dasatinib and the copolymer.

17. The treatment regimen of claim 7 , wherein the copolymer is insoluble in an aqueous medium at pH of 5 or lower, and soluble in an aqueous medium at pH 5.5 or greater.

18. The treatment regimen of claim 15 , wherein the one or more functional components is selected from one or more antioxidants that are present in an amount of 0.001% to 2% by weight of the amorphous solid dispersion.

19. The treatment regimen of claim 18 , wherein the one or more antioxidants comprises propyl gallate.

20. The treatment regimen of claim 7 , wherein the dasatinib and the copolymer are present in the amorphous solid dispersion in a w/w ratio of 40:60 to 70:30 (dasatinib:copolymer).

21. The treatment regimen of claim 7 , wherein the pharmaceutical composition comprises the amorphous solid dispersion and one or more pharmaceutically acceptable additives.

22. The treatment regimen of claim 7 , wherein the pharmaceutical composition is a solid dosage form suitable for oral administration.

23. The treatment regimen of claim 7 , wherein the pharmaceutical composition is a gastric acid-insensitive composition.

24. The method of claim 1 , wherein the copolymer is insoluble in an aqueous medium at pH of 5 or lower, and soluble in an aqueous medium at pH 5.5 or greater.

25. The method of claim 5 , wherein the one or more functional components is selected from one or more antioxidants that are present in an amount of 0.001% to 2% by weight of the amorphous solid dispersion.

26. The method of claim 25 , wherein the one or more antioxidants comprises propyl gallate.

27. The method of claim 1 , wherein the dasatinib and the copolymer are present in the amorphous solid dispersion in a w/w ratio of 40:60 to 70:30 (dasatinib:copolymer).

28. The method of claim 1 , wherein the pharmaceutical composition comprises the amorphous solid dispersion and one or more pharmaceutically acceptable additives.

29. The method of claim 1 , wherein the pharmaceutical composition is a solid dosage form suitable for oral administration.

30. The method of claim 1 , wherein the pharmaceutical composition is a gastric acid-insensitive composition.