Co-crystal of ketoprofen, lysine and gabapentin, pharmaceutical compositions and their medical use

Patent metadata

Field	Value
Publication number	US-12365644-B2
Application number	US-202117922999-A
Country	US
Kind code	B2
Filing date	May 4, 2021
Priority date	May 4, 2020
Publication date	Jul 22, 2025
Grant date	Jul 22, 2025

Abstract

The present invention relates to a new co-crystal of Ketoprofen, Lysine and Gabapentin, to pharmaceutical compositions and to their use in the prevention, reduction or treatment of pain and/or inflammation.

First claim

The invention claimed is:

1. A co-crystal of Ketoprofen, Lysine and Gabapentin, wherein the molar ratio of the components is 1:1:2.

2. The co-crystal according to claim 1 , characterized by the following XRPD diffraction peaks: 3.6, 6.3, 18.6 and 21.7 degrees 2-theta±0.2 degrees 2-theta.

3. The co-crystal according to claim 2 , further characterized by the following XRPD diffraction peaks: 9.6, 17.2 and 20.5 degrees 2-theta±0.2 degrees 2-theta.

4. The co-crystal according to claim 1 , further characterized by one or more of the following:
a DSC thermogram with the endothermic peak corresponding to the melting point at about 143.5° C. as shown in FIG. 3 ,
solution 1 H-NMR signals shown in FIG. 7 , and
solid state 13 C CPMAS signals as shown in FIG. 8 .

5. The co-crystal according to claim 1 , wherein the Ketoprofen is (S)-Ketoprofen and/or the Lysine is(S)-Lysine.

6. A method for the prevention, reduction or treatment of pain and/or inflammation in a subject in need thereof, comprising administration of the co-crystal according to claim 1 , alone or in combination with one or more pharmaceutically acceptable excipients.

7. The method according to claim 6 , wherein the pain is acute or chronic pain.

8. The method according to claim 6 , wherein the pain is selected from headache, toothache, menstrual pain, muscle pain, neuropathic pain, pain associated to neuroinflammation, diabetic neuropathy, cancer pain, osteoarthritis, low back pain, sciatalgia, fibromyalgia, trigeminal neuralgia; post-surgical and post-operative pain, post herpetic neuralgia, rheumatoid arthritis, ankylosing spondylitis, frozen shoulder, phantom limb pain or HIV pain.

9. A pharmaceutical composition comprising the co-crystal according to claim 1 and a least one pharmaceutically acceptable excipient.

10. The pharmaceutical composition according to claim 9 , which contains 0.5-60% by weight of the co-crystal and 40-99.5% by weight of one or more pharmaceutically acceptable excipients.

11. The pharmaceutical composition according to claim 9 , which is a solid composition for oral administration.

12. The pharmaceutical composition according to claim 10 , which is a solid composition for oral administration.

13. A process for the preparation of the co-crystal according to claim 1 , which comprises:
a) suspending Ketoprofen, Lysine and Gabapentin, in a molar ratio of 1/1 to 1.5/2 to 2.5, in a suitable solvent,
b) dissolving Ketoprofen, Lysine and Gabapentin, optionally by heating the suspension and/or under stirring, till a clear solution is obtained
c) subsequently cooling the solution, and
d) optionally adding an anti-solvent.

14. The process according to claim 13 , wherein the Ketoprofen and Lysine in step a) are in form of a Ketoprofen Lysine salt or a co-crystal.

15. The process according to claim 13 , wherein the Ketoprofen is the free acid and/or the Lysine is in neutral form.

16. The process according to claim 13 , wherein the Gabapentin is in neutral form (zwitterionic internal salt).

17. The process according to claim 13 , wherein in step a) the molar ratio of Gabapentin vs Ketoprofen is between 2:1 and 2.2:1.

18. The process according to claim 17 , wherein in step a) the molar ratio of Gabapentin vs Ketoprofen is about 2:1.

Assignees

• Dompe Farm Spa

Inventors

• Aramini Andrea
• Allegretti Marcello
• Bianchini Gianluca
• Lillini Samuele
• Tomassetti Mara

Classifications

• C07C229/28

  the carbon skeleton being saturated and containing rings · CPC title

• C07C229/26

  having more than one amino group bound to the carbon skeleton, e.g. lysine · CPC title

• C07B2200/13

  Crystalline forms, e.g. polymorphs · CPC title

• C07C2601/14

  The ring being saturated · CPC title

• C07C59/84 Primary

  containing six membered aromatic rings · CPC title