Nicotine salts, co-crystals, and salt co-crystal complexes

Patent metadata

Field	Value
Publication number	US-10865192-B2
Application number	US-201916598417-A
Country	US
Kind code	B2
Filing date	Oct 10, 2019
Priority date	May 27, 2014
Publication date	Dec 15, 2020
Grant date	Dec 15, 2020

Abstract

The invention provides certain nicotine salts, co-crystals, and salt co-crystals and provides novel polymorphic forms of certain nicotine salts. In particular, nicotine salts with orotic acid are described. The invention further provides methods of preparation and characterization of such nicotine salts. In addition, tobacco products, including smoking articles, smokeless tobacco products, and electronic smoking articles comprising nicotine salts, co-crystals, and/or salt co-crystals are also provided.

First claim

What is claimed:

1. A salt of nicotine and fumaric acid, wherein the salt is a non-solvated mono-salt, characterized by an X-ray powder diffraction pattern having peaks at one or more of the following 2-theta diffraction angles: 14.9, 18.4, 19.9, and 22.4.

2. A metastable polymorph of the salt of claim 1 , characterized by a different X-ray powder diffraction pattern that converts to the X-ray powder diffraction having peaks at one or more of the following 2-theta diffraction angles: 14.9, 18.4, 19.9, and 22.4 upon drying.

3. The salt of claim 1 , wherein at least about 50% of the salt is in crystalline form.

4. A method of preparing the salt of claim 1 , comprising combining nicotine and fumaric acid to form a solid and isolating the solid.

5. The method of claim 4 , wherein the combining comprises:
grinding the nicotine and fumaric acid;
mixing the nicotine and fumaric acid in ethyl acetate; or
mixing the fumaric acid in neat nicotine and using an anti-solvent selected from the group consisting of TBME, heptane, hexane, THF, DCM, ethyl acetate, MEK, IPA, or combinations thereof.

6. A method of preparing the metastable polymorph of claim 1 , comprising mixing fumaric acid in neat nicotine to form a solid, and isolating the solid.

7. The salt of claim 1 , wherein at least about 70% of the salt is in crystalline form.

8. The salt of claim 1 , wherein at least about 80% of the salt is in crystalline form.

9. The salt of claim 1 , wherein at least about 90% of the salt is in crystalline form.

10. The salt of claim 1 , characterized by an X-ray powder diffraction pattern having peaks at two or more of the following 2-theta diffraction angles: 14.9, 18.4, 19.9, and 22.4.

11. The salt of claim 1 , characterized by an X-ray powder diffraction pattern having peaks at three or more of the following 2-theta diffraction angles: 14.9, 18.4, 19.9, and 22.4.

12. The salt of claim 1 , characterized by an X-ray powder diffraction pattern having peaks at all of the following 2-theta diffraction angles: 14.9, 18.4, 19.9, and 22.4.

13. The salt of claim 1 , in a form comprising a white solid.

14. The salt of claim 1 , having a nicotine:fumaric acid ratio as measured by 1 H NMR of about 1:1.1.

15. The salt of claim 1 , having a nicotine:fumaric acid ratio as measured by 1 H NMR of about 1:1.2.

16. The salt of claim 1 , having a nicotine:fumaric acid ratio as measured by NMR of 1:1.4.

17. The salt of claim 1 , having a nicotine:fumaric acid ratio as measured by NMR of 1:1.0.

18. The salt of claim 1 , exhibiting an endotherm onset at 89° C.

19. The salt of claim 1 , wherein the X-ray powder diffraction pattern further comprises peaks at one or more of the following 2-theta diffraction angles: 17.5, 22.6, and 24.4.

Assignees

• Reynolds Tobacco Co R

Inventors

• Dull Gary M
• Carr Andrew
• Sharp Emma

Classifications

• A24F40/40

  Constructional details, e.g. connection of cartridges and battery parts · CPC title

• A24F40/10

  Devices using liquid inhalable precursors · CPC title

• C07D401/04 Primary

  directly linked by a ring-member-to-ring-member bond · CPC title

• C07D239/52

  Two oxygen atoms · CPC title

• A61K9/0073

  Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy; (nasal sprays A61K9/0043; inhalation of vapours of volatile or heated drugs, e.g. essential oils or nicotine, A61K9/007; devices A61M) · CPC title