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 polymer or copolymer of N-vinylpyrrolidone, 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 without a detrimental reduction in the exposure of dasatinib;

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

2. The method of claim 1 , wherein the polymer or copolymer of N-vinylpyrrolidone includes polyvinylpyrrolidone.

3. The method of claim 1 , wherein the polymer or copolymer of N-vinylpyrrolidone includes a vinylpyrrolidone/vinyl acetate copolymer.

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

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

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

7. 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.

8. The method of claim 7 , wherein the amorphous solid dispersion includes one or more solubilizers.

9. The method of claim 8 , wherein the one or more solubilizers comprises polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer.

10. The method of claim 1 , wherein the amorphous solid dispersion consists of dasatinib and the polymer or copolymer of N-vinylpyrrolidone.

11. The method of claim 1 , wherein the dasatinib and the polymer or copolymer of N-vinylpyrrolidone are present in the amorphous solid dispersion in a w/w ratio of 40:60 to 70:30 (dasatinib:(co)polymer).

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

13. The method of claim 12 , wherein the one or more pharmaceutically acceptable additives includes one or more solubilizers.

14. The method of claim 13 , wherein the one or more solubilizers comprises polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer.

15. The method of claim 1 , wherein the dasatinib is in the amorphous solid dispersion as dasatinib free base or dasatinib hydrochloride.

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

17. 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 vinylpyrrolidone/vinyl acetate copolymer, 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);

wherein the therapeutically effective amount comprises 20 mg to 140 mg dasatinib; and

wherein the second dose provides a therapeutically relevant exposure of dasatinib to the patient.

18. The treatment regimen of claim 17 , wherein the first dose comprises a standard dosage of a proton pump inhibitor.

19. The treatment regimen of claim 17 , 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.

20. The treatment regimen of claim 17 , wherein the first dose comprises a standard dosage of an H 2 antagonist.

21. The treatment regimen of claim 17 , wherein the first dose comprises a standard dosage of an H 2 antagonist selected from famotidine, cimetidine, nizatidine, ranitidine, or a combination thereof.

22. The treatment regimen of claim 17 , wherein the second dose is administered within 8 hours after the first dose.

23. The treatment regimen of claim 17 , wherein the second dose is administered within 6 hours after the first dose.

24. The treatment regimen of claim 17 , wherein the second dose is administered within 4 hours after the first dose.

25. The treatment regimen of claim 17 , wherein the amorphous solid dispersion includes one or more functional components selected from the group consisting of antioxidants, wetting agents, and solubilizers.

26. The treatment regimen of claim 25 , wherein the amorphous solid dispersion includes one or more solubilizers.

27. The treatment regimen of claim 26 , wherein the one or more solubilizers comprises polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer.

28. The treatment regimen of claim 17 , wherein the amorphous solid dispersion consists of dasatinib and the copolymer.

29. The treatment regimen of claim 17 , 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).

30. The treatment regimen of claim 17 , wherein the dasatinib is in the amorphous solid dispersion as dasatinib free base or dasatinib hydrochloride.