Solid state forms of valbenazine
AssigneeAssia Chemical Industries Ltd.
InventorsAriel Mittelman, Sharona Shachan-Tov, Abed Masarwa, Rotem Sella-Erez, Jonathan Enav, Motti Erlich, Victoria Machtey, Maytal Piran, Marina Yarovoy, Sagit Azran, Einat Kisin-Finfer, Tamar Nidam
Life of this patent
Estimating the term…
Abstract
Solid state forms of Valbenazine, Valbenazine salts, processes for preparation thereof and pharmaceutical compositions thereof are disclosed. Processes for the preparation of Valbenazine and intermediates in the preparation thereof are further described.
Claims44
A solid state form of Valbenazine ditosylate selected from:
- (A) crystalline form T10, which is characterized by data selected from one or more of the following:
- (i) an XRPD pattern having peaks at 6.4, 8.0, 10.9, 15.9 and 22.4 degrees 2-theta±0.2 degrees 2-theta;
- (ii) an XRPD pattern as depicted in FIG. 15;
- (iii) a solid state 13C-NMR spectrum with peaks at 168.9, 165.5, 147.2, 106.0 and 75.6 ppm±0.2 ppm;
- (iv) a solid state 13C-NMR spectrum having the following chemical shift absolute differences from a peak at 53.0±1 ppm of 115.9, 112.5, 94.2, 53.0 and 22.6±0.1 ppm;
- (v) a solid state 13C-NMR spectrum substantially as depicted in FIG. 23;
- and combinations of any of (i)-(v);
- or
- (B) crystalline form T12, which is characterized by data selected from one or more of the following:
- (i) an XRPD pattern having peaks at 6.4, 7.6, 12.3, 15.2 and 24.9 degrees 2-theta±0.2 degrees 2-theta;
- (ii) an XRPD pattern as depicted in FIG. 16;
- (iii) a solid state 13C-NMR spectrum with peaks at 166.4, 148.1, 126.9, 109.5 and 73.1 ppm±0.2 ppm;
- (iv) a solid state 13C-NMR spectrum having the following chemical shift absolute differences from a peak at 54.5±1 ppm of 111.9, 93.6, 72.4, 55.0 and 18.6±0.1 ppm;
- (v) a solid state 13C-NMR spectrum substantially as depicted in FIG. 25;
- and combinations of any of (i)-(v).
A solid state form of Valbenazine ditosylate selected from:
- (A) Valbenazine ditosylate Me-THF solvate,
- (B) Valbenazine ditosylate THF-solvate,
- (C) Valbenazine ditosylate isobutanol-solvate.
A process for the chiral resolution of (±)-Tetrabenazine comprising combining (±)-Tetrabenazine with (−)-O,O′-Di-p-Toluoyl-L-Tartaric acid ((−)-DPTTA) to form (+)-Tetrabenazine-(−)-DPTTA salt.
A process for the preparation of (R,R,R)-Dihydrotetrabenazine comprising chiral resolution of (±)-Tetrabenazine using (−)-O,O′-Di-p-Toluoyl-L-Tartaric acid ((−)-DPTTA) as resolving agent.
(canceled)
A crystalline form of (+)-Tetrabenazine-(−)-DPTTA salt designated as form I characterized by data selected from one or more of the following:
- (i) an XRPD having peaks at 5.7, 7.1, 11.3, 17.7 and 19.1 degrees 2-theta±0.2 degrees 2-theta;
- and/or
- (ii) an XRPD pattern as depicted in FIG. 27.
A crystalline form of a Valbenazine salt selected from:
- (A) Valbenazine fumarate;
- (B) Valbenazine stearate;
- (C) Valbenazine palmitate;
- (D) Valbenazine sulfate;
- (E) Valbenazine mesylate.
Dependencies are inferred from the claim text.