Claims for Patent: 11,026,939

Summary for Patent: 11,026,939

Title:	High dosage valbenazine formulation and compositions, methods, and kits related thereto
Abstract:	Solid pharmaceutical compositions with high drug loading are provided. A formulation useful for the solid pharmaceutical composition includes valbenazine, or a pharmaceutically acceptable salt thereof, silicified microcrystalline cellulose, isomalt, hydroxypropyl methylcellulose, partially pregelatinized maize starch, and magnesium stearate.
Inventor(s):	Moore, Jr.; Richard Alexander (San Diego, CA), McClelland; Gregory A. (San Diego, CA), O{grave over ( )}Brien; Christopher F. (Vashon, WA)
Assignee:	Neurocrine Biosciences, Inc. (San Diego, CA)
Application Number:	17/074,278
Patent Claims:	1. A unit dosage form comprising: (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 ditosylate; silicified microcrystalline cellulose; isomalt; hydroxypropyl methylcellulose; partially pregelatinized maize starch; and magnesium stearate; wherein (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 ditosylate is present at a level ranging from about 20 mg to 160 mg as measured as the free base, and (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 ditosylate is present at a level of at least 30% by weight of the total weight of the unit dosage form. 2. The unit dosage form of claim 1, wherein (S)-2-amino-3-methyl-butyric acid (2R,3R,11bR)-3-isobutyl-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-2H-py- rido[2,1-a]isoquinolin-2-yl ester ditosylate is present at a level of about 20 mg as measured as the free base. 3. The unit dosage form of claim 1, wherein (S)-2-amino-3-methyl-butyric acid (2R,3R,11bR)-3-isobutyl-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-2H-py- rido[2,1-a]isoquinolin-2-yl ester ditosylate is present at a level of about 40 mg as measured as the free base. 4. The unit dosage form of claim 1, wherein (S)-2-amino-3-methyl-butyric acid (2R,3R,11bR)-3-isobutyl-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-2H-py- rido[2,1-a]isoquinolin-2-yl ester ditosylate is present at a level of about 60 mg as measured as the free base. 5. The unit dosage form of claim 1, wherein (S)-2-amino-3-methyl-butyric acid (2R,3R,11bR)-3-isobutyl-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-2H-py- rido[2,1-a]isoquinolin-2-yl ester ditosylate is present at a level of about 80 mg as measured as the free base. 6. The unit dosage form of claim 1, wherein (S)-2-amino-3-methyl-butyric acid (2R,3R,11bR)-3-isobutyl-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-2H-py- rido[2,1-a]isoquinolin-2-yl ester ditosylate is present at a level of about 100 mg as measured as the free base. 7. The unit dosage form of claim 1, wherein the unit dosage form is suitable for oral administration. 8. The unit dosage form of claim 1, wherein the unit dosage form is formulated for dosing once daily. 9. The unit dosage form of claim 1, wherein the unit dosage form is in a capsule form. 10. The unit dosage form of claim 9, wherein the capsule is a size 3 capsule or smaller. 11. The unit dosage form of claim 9, wherein the capsule is a size 2 capsule or smaller. 12. The unit dosage form of claim 9, wherein the capsule is a size 1 capsule or smaller. 13. The unit dosage form of claim 9, wherein (S)-2-amino-3-methyl-butyric acid (2R,3R,11bR)-3-isobutyl-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-2H-py- rido[2,1-a]isoquinolin-2-yl ester ditosylate is present at a level of about 40 mg as measured as the free base and the capsule is a size 2 capsule or smaller. 14. The unit dosage form of claim 9, wherein (S)-2-amino-3-methyl-butyric acid (2R,3R,11bR)-3-isobutyl-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-2H-py- rido[2,1-a]isoquinolin-2-yl ester ditosylate is present at a level of about 60 mg as measured as the free base and the capsule is a size 2 capsule or smaller. 15. The unit dosage form of claim 9, wherein (S)-2-amino-3-methyl-butyric acid (2R,3R,11bR)-3-isobutyl-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-2H-py- rido[2,1-a]isoquinolin-2-yl ester ditosylate is present at a level of about 80 mg as measured as the free base and the capsule is a size 1 capsule or smaller. 16. The unit dosage form of claim 1, wherein (S)-2-amino-3-methyl-butyric acid (2R,3R,11bR)-3-isobutyl-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-2H-py- rido[2,1-a]isoquinolin-2-yl ester ditosylate has a d(0.9) particle size distribution less than 100 .mu.m. 17. The unit dosage form of claim 1, wherein said dosage form comprises: about 40 wt % 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 ditosylate; about 25 wt % of silicified microcrystalline cellulose; about 20 wt % of isomalt; about 5 wt % of hydroxypropyl methylcellulose; about 7.5 wt % of partially pregelatinized maize starch; about 2.5 wt % of magnesium stearate; and the unit dosage form is in a capsule form that is a size 1 capsule or smaller. 18. The unit dosage form of claim 17, wherein the capsule is a size 2 capsule or smaller. 19. The unit dosage form of claim 17, wherein the unit dosage form is suitable for oral administration. 20. The unit dosage form of claim 17, wherein the unit dosage form is formulated for dosing once daily. 21. The unit dosage form of claim 17, wherein (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 ditosylate has a d(0.9) particle size distribution less than 100 .mu.m. 22. A method of treating a hyperkinetic movement disorder in a patient in need thereof, comprising administering to the patient the unit dosage form 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 administering to the patient the unit dosage form of claim 17. 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.