Cocrystal of varenicline and oxalic acid, pharmaceutical composition thereof, and methods of use thereof
Provided is a cocrystal of varenicline and oxalic acid. In particular, provided is a cocrystal of varenicline and oxalic acid of formula (I) having a molar ratio of varenicline to oxalic acid of 1:1.5. Also provided is a process for preparing the cocrystal, a pharmaceutical composition containing the cocrystal and a method of using the cocrystal and pharmaceutical composition, such as for reducing nicotine addiction or tobacco use.
1. A cocrystal of varenicline and oxalic acid of formula (I):
wherein a molar ratio of varenicline to oxalic acid in the cocrystal is 1:1.5.
2. The cocrystal of claim 1 , characterized by an X-ray powder diffraction (XRPD) spectrum comprising diffraction peaks at diffraction angles (2θ±0.2°) of 5.718, 11.508, 11.973, 13.946, 15.549, 15.699, 18.026, 20.357, 26.213, and 26.603.
3. The cocrystal of claim 2 , further comprising diffraction peaks at diffraction angles (2θ±0.2°) of 9.866, 12.612, 17.382, 18.383, 19.602, 19.682, 21.251, 24.351, 23.895, 24.502, 27.559, 28.281, 29.283, 29.850, 31.150, 31.437, 31.781, 32.984, 34.188, 34.487, 34.699, 35.282, 35.530, 35.946, 38.118, and 38.526.
4. The cocrystal of claim 1 , wherein the cocrystal has an X-ray powder diffraction (XRPD) spectrum as shown in The FIGURE.
5. A process for producing the cocrystal of claim 1 , the process comprising:
(a) dissolving varenicline free base in a solvent, heating, and cooling to form a varenicline solution;
(b) dissolving oxalic acid dihydrate in the solvent to form an oxalic acid solution;
(c) adding the oxalic acid solution to the varenicline solution to form a reaction mixture; and
(d) stirring the reaction mixture at room temperature to precipitate the cocrystal.
6. A process for producing the cocrystal of claim 2 , the process comprising:
(a) dissolving varenicline free base in a solvent, heating, and cooling to form a varenicline solution;
(b) dissolving oxalic acid dihydrate in the solvent to form an oxalic acid solution;
(c) adding the oxalic acid solution to the varenicline solution to form a reaction mixture; and
(d) stirring the reaction mixture at room temperature to precipitate the cocrystal.
7. A process for producing the cocrystal of claim 4 , the process comprising:
(a) dissolving varenicline free base in a solvent, heating, and cooling to form a varenicline solution;
(b) dissolving oxalic acid dihydrate in the solvent to form an oxalic acid solution;
(c) adding the oxalic acid solution to the varenicline solution to form a reaction mixture; and
(d) stirring the reaction mixture at room temperature to precipitate the cocrystal.
8. A pharmaceutical composition comprising the cocrystal of claim 1 and a pharmaceutically acceptable carrier.
9. A pharmaceutical composition comprising the cocrystal of claim 2 and a pharmaceutically acceptable carrier.
10. A pharmaceutical composition comprising the cocrystal of claim 4 and a pharmaceutically acceptable carrier.
11. A method of reducing nicotine addiction or tobacco use in a subject in need thereof, the method comprising administering to the subject the pharmaceutical composition of claim 8 .
12. A method of reducing nicotine addiction or tobacco use in a subject in need thereof, the method comprising administering to the subject the pharmaceutical composition of claim 9 .
13. A method of reducing nicotine addiction or tobacco use in a subject in need thereof, the method comprising administering to the subject the pharmaceutical composition of claim 10 .