Analogs of deutetrabenazine, their preparation and use
The disclosure is directed to deutetrabenazine analogs, compositions comprising same and methods of detecting same in compositions comprising deutetrabenazine.
1. A pharmaceutical composition in the form of a tablet comprising an admixture of a deutetrabenazine drug substance and a pharmaceutically acceptable carrier, wherein the deutetrabenazine drug substance comprises 5 mg to 30 mg of deutetrabenazine; and
Compound 2 in an amount that is not more than 0.15 area %, relative to the concentration of the deutetrabenazine in the tablet, based on a determination by an HPLC method comprising a C18, 150×4.6 mm, 3.5 μm column and a photodiode array/ultraviolet detector at 220 nm
2. The pharmaceutical composition of claim 1 , wherein the concentration of the Compound 2 does not increase to more than 0.4 area-% relative to the concentration of the deutetrabenazine in the tablet, based on a determination by the HPLC method, after storage of the tablet at room temperature for twenty-four months.
3. The pharmaceutical composition of claim 1 , wherein the concentration of the Compound 2 is 0.3 area-% or less, relative to the concentration of the deutetrabenazine in the tablet, based on a determination by the HPLC method, after storage of the tablet at room temperature for one month.
4. The pharmaceutical composition of claim 1 , comprising 0.25 area-% or less of the Compound 2, relative to the concentration of the deutetrabenazine in the tablet, based on a determination by the HPLC method, after storage of the tablet at room temperature for one month.
5. The pharmaceutical composition of claim 1 , wherein the concentration of the Compound 2 is 0.2 area-% or less, relative to the concentration of the deutetrabenazine in the tablet, based on a determination by the HPLC method, after storage of the tablet at room temperature for one month.
6. The pharmaceutical composition of claim 1 , comprising 6-24 mg deutetrabenazine.
7. The pharmaceutical composition of claim 1 , prepared for once daily administration.
8. The pharmaceutical composition of claim 1 , prepared for more than once daily administration.
9. A method of treating a subject afflicted with a hyperkinetic movement disorder comprising administering to the subject the pharmaceutical composition of claim 1 .
10. The method of claim 9 , wherein the hyperkinetic movement disorder is Huntington's disease.
11. The method of claim 9 , wherein the hyperkinetic movement disorder is chorea related to Huntington's disease.
12. The method of claim 9 , wherein the hyperkinetic movement disorder is tardive dyskinesia.
13. The method of claim 9 , wherein the hyperkinetic movement disorder is a tic associated with Tourette syndrome.
14. The pharmaceutical composition of claim 1 , comprising 6 mg of deutetrabenazine.
15. The pharmaceutical composition of claim 1 , comprising 9 mg of deutetrabenazine.
16. The pharmaceutical composition of claim 1 , comprising 12 mg of deutetrabenazine.
17. The pharmaceutical composition of claim 1 , comprising 24 mg of deutetrabenazine.
18. The pharmaceutical composition of claim 1 , wherein the concentration of the Compound 2 does not increase to more than 0.4 area-% relative to the concentration of the deutetrabenazine in the tablet, based on a determination by the HPLC method, after storage of the tablet at room temperature for two months.
19. The pharmaceutical composition of claim 1 , wherein the concentration of the Compound 2 does not increase to more than 0.4 area-% relative to the concentration of the deutetrabenazine, based on a determination by the HPLC method, after storage at room temperature for three months.
20. The pharmaceutical composition of claim 1 , wherein the concentration of the Compound 2 does not increase to more than 0.4 area-% relative to the concentration of the deutetrabenazine, based on a determination by the HPLC method, after storage at room temperature for six months.
21. The pharmaceutical composition of claim 1 , wherein the concentration of the Compound 2 is 0.4 area-% or less, relative to the concentration of the deutetrabenazine, based on a determination by the HPLC method, after storage at room temperature for one month.
22. The pharmaceutical composition of claim 1 , comprising 18 mg of deutetrabenazine.