Crystals of laquinimod sodium, and process for the manufacture thereof

• US 7,884,208 B2
• Filed: 10/18/2006
• Issued: 02/08/2011
• Est. Priority Date: 10/19/2005
• Status: Expired due to Fees

• Current Assignee: Teva Pharmaceutical Industries Limited
• Original Assignee: Teva Pharmaceutical Industries Limited
• Inventors: Frenkel, Anton, Laxer, Avital, Gurevich, Eduard
• Primary Examiner(s): Krass; Frederick
• Assistant Examiner(s): Simmons; Chris E
• Application Number:
  US11/583,282
• Publication Number:
  US 20070088050A1
• Time in Patent Office: 1,574 Days
• Field of Search: 514/312, 546/156
• US Class Current: 546/156
• CPC Class Codes: A61K 31/4704 2-Quinolinones, e.g. carbostyril
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07D 215/54 attached in position 3
• CPC Class Codes: C07D 215/56 with oxygen atoms in position 4

Abstract

Disclosed is a process for the preparation of laquinimod sodium which removes the impurities after the salt formation step, thus resulting in crystals of higher purity as well as crystals having improved crystalline characteristics.

Claims

1. A mixture of crystalline laquinimod sodium particles, wherein 10% or more of the total amount by volume of the laquinimod sodium particles have a size of greater than 40 microns and wherein the mixture has a bulk density of at least 0.4 g/mL.

2. The mixture of claim 1, wherein 50% or more of the total amount by volume of the laquinimod sodium particles have a size of greater than 15 microns.

3. The mixture of claim 1, having a tapped density of at least 0.6 g/mL.

4. The mixture of claim 1, having a tapped density of less than 0.8 g/mL.

5. The mixture of any of claim 1, comprising no more than 2 ppm of a heavy metal.

6. The mixture of claim 5, wherein the heavy metal is iron, nickel or chromium.

7. A pharmaceutical composition comprising the mixture of claim 1 and a pharmaceutically acceptable carrier.

8. The pharmaceutical composition of claim 7 in the form of a tablet or capsule.