Crystalline form of Eluxadoline

Patent metadata

Field	Value
Publication number	US-10822309-B2
Application number	US-201916683331-A
Country	US
Kind code	B2
Filing date	Nov 14, 2019
Priority date	Sep 25, 2017
Publication date	Nov 3, 2020
Grant date	Nov 3, 2020

Abstract

The present invention provides a novel crystalline form of Eluxadoline, Eluxadoline Form APO-I, a co-crystal of Eluxadoline and methyl nicotinate, compositions and processes for the preparation thereof, and the use of this crystalline form in the treatment of opioid-modulated disorders, and in particular, gastrointestinal disorders, including irritable bowel syndrome with diarrhea (IBS-D).

First claim

What is claimed is:

1. A solid pharmaceutical composition comprising a crystalline form of Eluxadoline that is a co-crystal of Eluxadoline and methyl nicotinate characterized by a PXRD diffractogram comprising peaks, expressed in degrees 2θ (±0.2°), at 6.4°, 6.9°, and 11.4°, and one or more pharmaceutically acceptable excipients.

2. The pharmaceutical composition of claim 1 , wherein the crystalline form of Eluxadoline further comprises at least three peaks, expressed in degrees 2θ (±0.2°), selected from the group consisting of: 8.7°, 9.9°, 12.7°, 14.8°, 15.8°, 17.5°, 18.9°, 19.8°, and 23.8°.

3. The pharmaceutical composition of claim 1 , wherein the crystalline form of Eluxadoline further comprises peaks, expressed in degrees 2θ (±0.2°), at 8.7°, 9.9°, 12.7°, 14.8°, 15.8°, 17.5°, 18.9°, 19.8°, and 23.8°.

4. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition is in the form of a solid dosage form.

5. The pharmaceutical composition of claim 4 , wherein the pharmaceutical composition is a tablet.

6. The pharmaceutical composition of claim 1 , wherein a molar ratio of Eluxadoline to methyl nicotinate in the crystalline form is between approximately 1:0.5 and approximately 1:1.5.

7. The pharmaceutical composition of claim 1 , wherein a molar ratio of Eluxadoline to methyl nicotinate in the crystalline form is approximately 1:1.

8. The pharmaceutical composition of claim 5 , wherein the co-crystal of Eluxadoline and methyl nicotinate is present in an amount equivalent to 75 mg of Eluxadoline.

9. The pharmaceutical composition of claim 5 , wherein the co-crystal of Eluxadoline and methyl nicotinate is present in an amount equivalent to 100 mg of Eluxadoline.

Assignees

• Apotex Inc

Inventors

• Souza Fabio E S
• Khalili Bahareh
• Bhattacharyya Annyt

Classifications

• C07B2200/13

  Crystalline forms, e.g. polymorphs · CPC title

• A61K9/20

  Pills, tablets, {discs, rods (A61K9/0004, A61K9/0007, A61K9/0056, A61K9/0065 take precedence; for reconstitution of a drink A61K9/0095)} · CPC title

• C07D233/64 Primary

  with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine · CPC title

• A61K31/4164

  1,3-Diazoles · CPC title

• A61P1/12

  Antidiarrhoeals · CPC title