High dosage valbenazine formulation and compositions, methods, and kits related thereto

1. A solid pharmaceutical composition comprising:

a ditosylate salt of (S)-2-amino-3-methyl-butyric acid (2R,3R,11bR)-3-isobutyl-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-yl ester;

at least one water-insoluble filler;

at least one water-soluble diluent;

at least one binder;

at least one disintegrant; and

at least one lubricant,

wherein the ditosylate salt is present in the solid pharmaceutical composition at a level of at least 30% by weight of the solid pharmaceutical composition.

2. The solid pharmaceutical composition of claim 1 , wherein the ditosylate salt is present in the solid pharmaceutical composition at a level of at least 35% by weight of the solid pharmaceutical composition.

3. The solid pharmaceutical composition of claim 1 , wherein the ditosylate salt is present in the solid pharmaceutical composition at a level of at least 38% by weight of the solid pharmaceutical composition.

4. The solid pharmaceutical composition of claim 1 , wherein the ditosylate salt is present in the solid pharmaceutical composition at a level of at least 40% by weight of the solid pharmaceutical composition.

5. The solid pharmaceutical composition of claim 1 , wherein said dosage form comprises:

between 20% w/w and 40% w/w of the at least one water-insoluble filler;

between 20% w/w and 40% w/w of the at least one water-soluble diluent;

between 0.5% w/w and 5% w/w of the at least one binder;

between 1% w/w and 10% w/w of the at least one disintegrant; and

between 0.25% w/w and 5% w/w of the at least one lubricant.

6. The solid pharmaceutical composition of claim 5 , wherein the at least one water-insoluble filler is microcrystalline cellulose.

7. The solid pharmaceutical composition of claim 5 , wherein the at least one water-soluble diluent is isomalt.

8. The solid pharmaceutical composition of claim 5 , wherein the binder is hypromellose.

9. The solid pharmaceutical composition of claim 5 , wherein the at least one disintegrant is partially pregelatinized maize starch.

10. The solid pharmaceutical composition of claim 5 , wherein the at least one lubricant is magnesium stearate.

11. The solid pharmaceutical composition of claim 5 , wherein the at least one water-insoluble filler is microcrystalline cellulose and is present in an amount of about 25% w/w.

12. The solid pharmaceutical composition of claim 5 , wherein the at least one water-soluble diluent is isomalt and is present in an amount of about 20% w/w.

13. The solid pharmaceutical composition of claim 5 , wherein the at least one binder is hypromellose and is present in an amount of about 5% w/w.

14. The solid pharmaceutical composition of claim 5 , wherein the at least one disintegrant is partially pregelatinized maize starch and is present in an amount of about 7.5% w/w.

15. The solid pharmaceutical composition of claim 5 , wherein the at least one lubricant is magnesium stearate and is present in an amount of about 2.5% w/w.

16. The solid pharmaceutical composition of claim 1 , wherein the solid pharmaceutical composition is suitable for oral administration.

17. The solid pharmaceutical composition of claim 1 , wherein the solid pharmaceutical composition has a bulk density of at least about 0.5 mg/mL.

18. The solid pharmaceutical composition of claim 1 , wherein the solid pharmaceutical composition has a tapped density of at least about 0.6 mg/mL.

19. The solid pharmaceutical composition of claim 1 , wherein the solid pharmaceutical composition has a blend uniformity between about 90% and about 110% with a relative standard deviation of the blend uniformity of less than about 2%.

20. The solid pharmaceutical composition of claim 1 , wherein the ditosylate salt has a d(0.9) particle size distribution less than 100 μm.

21. The solid pharmaceutical composition of claim 1 , wherein:

the ditosylate salt is present in the solid pharmaceutical composition at a level of at least 38% by weight of the solid pharmaceutical composition;

the at least one water-insoluble filler is microcrystalline cellulose and is present in an amount of about 25% w/w;

the at least one water-soluble diluent is isomalt and is present in an amount of about 20% w/w;

the at least one binder is hypromellose and is present in an amount of about 5% w/w;

the at least one disintegrant is partially pregelatinized maize starch and is present in an amount of about 7.5% w/w; and

the at least one lubricant is magnesium stearate and is present in an amount of about 2.5% w/w.

22. A method of treating a hyperkinetic movement disorder in a patient in need thereof, comprising orally administering to the patient the solid pharmaceutical composition of claim 1 .

23. The method according to claim 22 , wherein the hyperkinetic movement disorder is tardive dyskinesia.

24. The method according to claim 22 , wherein the hyperkinetic movement disorder is chorea.

25. The method according to claim 24 , wherein chorea is associated with Huntington's disease.

26. A method of treating a hyperkinetic movement disorder in a patient in need thereof, comprising orally administering to the patient the solid pharmaceutical composition of claim 21 .

27. The method according to claim 26 , wherein the hyperkinetic movement disorder is tardive dyskinesia.

28. The method according to claim 26 , wherein the hyperkinetic movement disorder is chorea.

29. The method according to claim 28 , wherein chorea is associated with Huntington's disease.

30. The solid pharmaceutical composition of claim 1 , wherein the solid pharmaceutical composition comprises granules, wherein the granules comprise the ditosylate salt.

31. The solid pharmaceutical composition of claim 5 , wherein the solid pharmaceutical composition comprises granules, wherein the granules comprise the ditosylate salt.

32. The solid pharmaceutical composition of claim 21 , wherein the solid pharmaceutical composition comprises granules, wherein the granules comprise the ditosylate salt.