SOLID FORMS OF ENANTIOPURE DEUTERIUM-ENRICHED BUPROPION AND METHODS OF USE THEREOF
The present disclosure provides a crystalline form of enantiopure deuterium-enriched bupropion, pharmaceutical compositions, and methods of treating mood disorders, neurological disorders, movement disorders, cardiovascular disorders, metabolic disorders, and other disorders using a crystalline form of enantiopure deuterium-enriched bupropion.
1 . A crystalline form of a compound represented by Formula (I):
wherein R 1 , R 2 , and R 3 are each independently H or D, provided that the abundance of deuterium in each of R 1 , R 2 , and R 3 is at least 30%, and wherein the crystalline form of the compound is characterized by an X-ray powder diffraction pattern comprising peaks at the following diffraction angles (2θ): 12.3°±0.2°, 15.3°±0.2°, and 15.8°±0.2°.
2 . The crystalline form of claim 1 , wherein the crystalline form of the compound is characterized by an X-ray powder diffraction pattern further comprising one or more peaks at the following diffraction angles (2θ): 13.4°±0.2°, 14.1°±0.2°, 16.9°±0.2°, 17.3°±0.2°, 18.4°±0.2, 18.8°±0.2°, 22.0°±0.2° and 22.8°±0.2°.
3 . The crystalline form of claim 1 , wherein the crystalline form of the compound is characterized by an X-ray powder diffraction pattern substantially the same as shown in FIG. 3 .
4 . The crystalline form of claim 1 , wherein the crystalline form of the compound has a melting point onset as determined by differential scanning calorimetry at about 225° C. to about 235° C.
5 . The crystalline form of claim 1 , wherein the crystalline form of the compound is characterized by a differential scanning calorimetry pattern substantially the same as shown in FIG. 5 .
6 . The crystalline form of claim 1 , wherein the crystalline form of the compound is anhydrous.
7 . The crystalline form of claim 1 , wherein the abundance of deuterium in R 1 is at least 50%.
8 . The crystalline form of claim 1 , wherein the abundance of deuterium in R 2 is at least 50%.
9 . The crystalline form of claim 1 , wherein the abundance of deuterium in R 3 is at least 50%.
10 . The crystalline form of claim 1 , wherein the abundance of deuterium in each of R 1 , R 2 , and R 3 is at least 50%.
11 . The crystalline form of claim 1 , wherein the abundance of deuterium in each of R 1 , R 2 , and R 3 is at least 75%.
12 . The crystalline form of claim 1 , wherein the abundance of deuterium in each of R 1 , R 2 , and R 3 is at least 90%.
13 . The crystalline form of claim 1 , wherein the abundance of deuterium in each of R 1 , R 2 , and R 3 is at least 95%.
14 . The crystalline form of claim 1 , wherein the crystalline form of the compound is characterized by a stereochemical purity of at least 75% enantiomeric excess at the carbon bearing variable R 1 .
15 . The compound of claim 1 , wherein the crystalline form of the compound is characterized by a stereochemical purity of at least 90% enantiomeric excess at the carbon bearing variable R 1 .
16 . The compound of claim 1 , wherein the crystalline form of the compound is characterized by a stereochemical purity of at least 95% enantiomeric excess at the carbon bearing variable R 1 .
17 . A pharmaceutical composition comprising a crystalline form of the compound of claim 1 , and a pharmaceutically acceptable excipient.