Pharmaceutical compositions for the treatment of cystic fibrosis transmembrane conductance regulator mediated diseases

Claims

PATENT REQUESTS 1. A pharmaceutical composition, characterized in that it contains: a first spray-dried dispersion and a second spray-dried dispersion, wherein the first spray-dried dispersion contains about 70% by weight to about 90% by weight of the amorphous form of (R)- 1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-N-(1-(2,3-dihydropropyl)-6-fluoro-2-(1-hydroxy-2-methylpropan-2-yl)- 1H-indol-5-yl)cyclopropanecarboxamide (Compound 1) and about 10% by weight to about 30% by weight of the polymer, and wherein the second spray-dried dispersion comprises an amorphous form of N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4- dihydro-4-oxoquinoline-3-carboxamide (Compound 2); and wherein the pharmaceutical composition is a tablet.

2. The pharmaceutical composition according to claim 1, wherein the polymer comprises a cellulose polymer.

3. A pharmaceutical composition according to claim 1 or claim 2, characterized in that the polymer comprises hydroxypropylmethyl cellulose.

4. The pharmaceutical composition of claim 1, wherein the second spray-dried dispersion further comprises contains polymer.

5. The pharmaceutical composition according to claim 4, wherein the second spray-dried dispersion comprises about 70% by weight to about 90% by weight of Compound 2 and about 10% by weight to about 30% by weight of polymer.

6. A pharmaceutical composition according to any one of claims 1 to 5, characterized in that it contains about 5% by weight up to about 20% by mass of the first spray-dried dispersion.

7. A pharmaceutical composition according to any one of claims 1 to 6, characterized in that it contains about 15% by weight up to about 60% by weight of the second spray-dried dispersion.

8. A pharmaceutical composition according to any one of claims 1 to 7, characterized in that the tablet contains about 25 mg to about 125 mg of Compound 1.

9. A pharmaceutical composition according to any one of claims 1 to 8, characterized in that the tablet contains about 100 mg to about 200 mg of Compound 2.

10. A pharmaceutical composition according to any one of claims 1 to 9, characterized in that the pharmaceutical composition contains one or more excipients selected from fillers, disintegrators, lubricants, or any of them combinations.

11. A pharmaceutical composition according to any one of claims 1 to 7, characterized in that it contains about 30% by weight up to about 50% by weight of the filler relative to the weight of the pharmaceutical composition.

12. Pharmaceutical composition according to claim 11, characterized in that the filler comprises microcrystalline cellulose.

13. A pharmaceutical composition according to any one of claims 1 to 12, characterized in that it contains about 1% by weight up to about 10% by mass of the disintegrator in relation to the mass of the pharmaceutical preparation.

14. A pharmaceutical composition according to claim 13, wherein the disintegrant comprises croscarmellose sodium.

15. A pharmaceutical composition according to any one of claims 1 to 14, characterized in that it contains about 1% by weight of lubricant relative to the weight of the pharmaceutical preparation.

16. The pharmaceutical composition according to claim 15, wherein the lubricant comprises magnesium stearate.

17. A pharmaceutical composition according to any one of claims 1 to 7, characterized in that the tablet contains about 30 mg to about 85 mg of the first spray-dried dispersion.

18. A pharmaceutical composition according to any one of claims 1 to 17, characterized in that the tablet contains about 150 mg to about 250 mg of the second spray-dried dispersion.

19. A pharmaceutical composition according to any one of claims 1 to 18, characterized in that the tablet contains about 100 mg to about 300 mg of filler.

20. A pharmaceutical composition according to any one of claims 1 to 19, characterized in that the tablet contains about 12 mg to about 36 mg of disintegrator.

21. A pharmaceutical composition according to any one of claims 1 to 20, characterized in that the tablet contains about 1 mg to about 5 mg of lubricant.

22. A pharmaceutical composition according to any one of claims 1 to 21, characterized in that it further comprises an additional therapeutic agent.

23. The pharmaceutical composition according to claim 22, wherein the additional therapeutic agent is another A CFTR corrector that is different from Compound 1.

24. The pharmaceutical composition according to claim 22, wherein the additional therapeutic agent is another A CFTR potentiator that is different from Compound 2.

25. A pharmaceutical composition according to any one of the preceding claims, characterized in that it is for use in the procedure for treating cystic fibrosis in a patient.

26. A pharmaceutical composition for use according to claim 25, wherein the method comprises oral administration. administering a pharmaceutical preparation to a patient.

27. A pharmaceutical composition for use according to any one of claims 25 or 26, wherein the process further comprising administering an additional therapeutic agent to the patient.

28. A pharmaceutical composition for use according to claim 27, wherein the additional therapeutic agent administered before, after, or simultaneously with the pharmaceutical composition.

29. A pharmaceutical composition for use according to any one of claims 25 to 28, wherein the patient is homozygous for CFTR mutation ∆F508.

30. A pharmaceutical composition for use according to any one of claims 25 to 28, wherein the patient is heterozygous for the CFTR mutation ∆F508.