Co-crystal of ketoprofen and its preparation, pharmaceutical compositions comprising the same and uses thereof

Patent metadata

Field	Value
Publication number	US-12528760-B2
Application number	US-202017787611-A
Country	US
Kind code	B2
Filing date	Dec 21, 2020
Priority date	Dec 23, 2019
Publication date	Jan 20, 2026
Grant date	Jan 20, 2026

Abstract

The present invention refers to a co-crystal of Ketoprofen Lysine named Form 4, a pharmaceutical composition comprising said co-crystal, a process for its preparation and to its use in the treatment of pain and inflammatory diseases.

First claim

The invention claimed is:

1 . A co-crystal of Ketoprofen Lysine (Form 4) characterized in that the co-crystal has an X-ray diffraction pattern with characteristic peaks at 13.6; 16.0; 16.5; 17.3; 19.1; 19.4; 20.5; 21.8; 22.9; 23.5; 24.9; 25.9; 27.6° 2theta±0.20 degrees.

2 . The co-crystal according to claim 1 , characterized by having the following X-ray diffraction pattern characteristic peaks: 3.8; 7.6; 11.4; 11.6; 13.4; 13.6; 14.6; 15.2; 15.5; 15.9; 16.0; 16.5; 17.3; 18.8; 18.9; 19.0; 19.1; 19.2; 19.3; 19.4; 20.5; 20.6; 21.7; 21.8; 21.9; 22.0; 22.1; 22.2; 22.3; 22.4; 22.9; 23.4; 23.5; 23.5; 24.1; 24.2; 24.4; 24.5; 24.6; 24.7; 24.9; 25.0; 25.3; 25.4; 25.5; 25.9; 26.0; 26.5; 26.5; 26.8; 26.9; 27.0; 27.1; 27.4; 27.6; 27.7; 27.8; 28.2; 28.3; 28.4; 29.0; 29.2; 29.3; 29.5; 29.9; 30.0; 30.7° 2theta±0.20 degrees.

3 . The co-crystal according to claim 1 , wherein the molecular ratio between Ketoprofen and Lysine is 1:1.

4 . The co-crystal according to claim 1 , characterized in that the co-crystal has an endothermic peak at 158.8° C.±2° C. measured by differential scanning calorimetry (DSC).

5 . The co-crystal according to claim 1 , wherein the co-crystal has a particle size distribution wherein D90 is lower than 220 μm.

6 . The co-crystal according to claim 1 , wherein the co-crystal has a particle size distribution wherein D90 is lower than 150 μm.

7 . A pharmaceutical composition comprising the co-crystal according to claim 1 and at least one physiologically acceptable excipient.

8 . The pharmaceutical composition according to claim 7 , wherein the excipients are selected from the group consisting of: povidone, colloidal silica, hydroxypropylmethylcellulose, copolymer of butyl methacrylate, dimethylaminoethyl methacrylate and methyl methacrylate, sodium dodecyl sulfate, stearic acid, magnesium stearate, aspartame, mannitol, xylitol, talc, and flavors.

9 . The pharmaceutical composition according to claim 7 , wherein the pharmaceutical composition is in solid granulate form.

10 . A pharmaceutical composition comprising the co-crystal according to claim 1 in combination with at least another pharmaceutically active ingredient.

11 . A method of treating a condition selected from pain and inflammation diseases in a subject in need thereof, comprising administration of the co-crystal according to claim 1 , alone or in combination with one or more physiologically acceptable excipients.

12 . The method according to claim 11 , wherein the pain is selected from the group consisting of: acute pain, headache, toothache, menstrual pain, muscle pain, and osteoarticular pain.

13 . The method according to claim 11 , wherein the inflammation diseases is rheumatitis disease.

14 . A process for the preparation of the co-crystal according to claim 1 , wherein the process comprises the following steps:
a) preparing a non-saturated solution of Ketoprofen in a solvent selected from 2-methyl-1-propanol and ethyl acetate; b) mixing the non-saturated solution of Ketoprofen with solid lysine to provide an admixture.

15 . The process according to claim 14 , wherein the non-saturated solution of step a) has a concentration of Ketoprofen from 50 to 150 mg/ml.

16 . The process according to claim 15 , wherein the non-saturated solution of step a) has a concentration of Ketoprofen from 70 to 120 mg/ml.

17 . The process according to claim 15 , wherein the non-saturated solution of step a) has a concentration of Ketoprofen from 80 to 100 mg/ml.

18 . The process according to claim 14 , wherein the molar ratio Ketoprofen:Lysine is from 1.5:1 to 3.5:1.

19 . The process according to claim 18 , wherein the molar ratio Ketoprofen:Lysine is from 2:1 to 3:1.

20 . The process according to claim 14 , wherein the admixture obtained in step b) has a water content from 0.3 to 1.5% (v/v).

21 . The process according to claim 20 , wherein the admixture obtained in step b) has a water content from 0.8% to 1.1% (v/v).

22 . The process according to claim 14 , wherein the solvent of step a) is 2-methyl-1-propanol.

Assignees

• Dompe Farm Spa

Inventors

• Aramini Andrea
• Bianchini Gianluca
• Lillini Samuele

Classifications

• C07B2200/13

  Crystalline forms, e.g. polymorphs · CPC title

• C07C57/30 Primary

  containing six-membered aromatic rings · CPC title

• C07C51/41 Primary

  Preparation of salts of carboxylic acids ({C07C51/093 - C07C51/34 take precedence} preparation of soap C11D) · CPC title