Tranexamic acid formulations

• US 8,273,795 B2
• Filed: 08/13/2008
• Issued: 09/25/2012
• Est. Priority Date: 03/04/2004
• Status: Active Grant

• Current Assignee: Amring Pharmaceuticals, Inc., Xenodyne Pharmaceuticals
• Original Assignee: Ferring BV (Ferring Holding SA)
• Inventors: Moore, Keith A., Heasley, Ralph A., Greiwe, Jeffrey S., Facemire, John W., Modest, Jason D.
• Primary Examiner(s): Rao, Savitha
• Application Number:
  US12/228,489
• Publication Number:
  US 20090048341A1
• Time in Patent Office: 1,504 Days
• Field of Search: 514/561, 514/574
• US Class Current: 514/574
• CPC Class Codes: A61K 31/19 Carboxylic acids, e.g. valproic acid salicylic acid A61K31/60
• CPC Class Codes: A61K 31/195 having an amino group
• CPC Class Codes: A61K 31/196 the amino group being directly attached to a ring, e.g. anthranilic acid, mefenamic acid, diclofenac, chlorambucil
• CPC Class Codes: A61K 9/2009 Inorganic compounds
• CPC Class Codes: A61K 9/2013 Organic compounds, e.g. phospholipids, fats
• CPC Class Codes: A61K 9/2027 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/2059 Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 7/04 Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents

Abstract

Disclosed are modified release oral tranexamic acid formulations and methods of treatment therewith.

Claims

1. A method of treating menorrhagia, the method comprising:

orally administering to a patient in need of such treatment a tranexamic acid formulation comprising;

tranexamic acid or a pharmaceutically acceptable salt thereof; and

a modified release material;

wherein the tranexamic acid or pharmaceutically acceptable salt thereof is present in an amount from about 50% to about 95% by weight of the formulation;

wherein the modified release material is present in an amount from about 5% to about 50% by weight of the formulation;

wherein the formulation is administered as two oral dosage forms, each providing a dose of about 650 mg of tranexamic acid; and

wherein said formulation provides an in-vitro dissolution release rate of the tranexamic acid or pharmaceutically acceptable salt thereof, when measured by a USP 27 Apparatus Type II Paddle Method @ 50 RPM in 900 ml water at 37±

0.5°

C., of less than about 40% by weight of the tranexamic acid or pharmaceutically acceptable salt thereof released at about 15 minutes, less than about 70% by weight of the tranexamic acid or pharmaceutically acceptable salt thereof released at about 45 minutes and not less than about 50% by weight of the tranexamic acid or pharmaceutically acceptable salt thereof released at about 90 minutes.

2. The method of claim 1, wherein said formulation provides an in-vitro dissolution release rate of the tranexamic acid or pharmaceutically acceptable salt thereof, when measured by the USP 27 Apparatus Type II Paddle Method @ 50 RPM in 900 ml water at 37±

0.5°

C., of about 0% to about 40% by weight of the tranexamic acid or pharmaceutically acceptable salt thereof released at about 15 minutes, from about 20% to about 60% by weight of the tranexamic acid or pharmaceutically acceptable salt thereof released at about 30 minutes, from about 40% to about 65% by weight of the tranexamic acid or pharmaceutically acceptable salt thereof released at about 45 minutes, from about 50% to about 95% by weight of the tranexamic acid or pharmaceutically acceptable salt thereof released at about 60 minutes, and not less than about 60% by weight of the tranexamic acid or pharmaceutically acceptable salt thereof released at about 90 minutes.

3. The method of claim 1, wherein the formulation releases about 10% to about 25% by weight of the tranexamic acid or pharmaceutically acceptable salt thereof every 15 minutes when measured in vitro utilizing the USP 27 Apparatus Type II Paddle Method @ 50 RPM in 900 ml water at 37±

0.5°

C.

4. The method of claim 1, wherein the formulation releases about 1% of the tranexamic acid or pharmaceutically acceptable salt thereof every minute when measured in-vitro utilizing the USP 27 Apparatus Type II paddle method at 50 RPM in 900 ml water at 37±

0.5°

C.

5. The method of claim 1, wherein the tranexamic acid or pharmaceutically acceptable salt thereof is tranexamic acid.

6. The method of claim 1, wherein a mean maximum plasma concentration (C_max) of tranexamic acid of from about 5 to about 17.5 mcg/ml is provided following the administration.

7. The method of claim 1, wherein the formulation is in the form of a matrix tablet which comprises a drug mixed together with a granulated modified release material.

8. The method of claim 1, wherein the tranexamic acid or pharmaceutically acceptable salt thereof is present in an amount from about 60% to about 90% by weight of the formulation.

9. The method of claim 1, wherein the tranexamic acid or pharmaceutically acceptable salt thereof is present in an amount from about 60% to about 80% by weight of the formulation.

10. The method of claim 1, wherein the modified release material is present in an amount from about 10% to about 35% by weight of the formulation.

11. The method of claim 1, wherein:

the tranexamic acid or pharmaceutically acceptable salt thereof is present in an amount from about 60% to about 90% by weight of the formulation;

the modified release material is present in an amount from about 10% to about 35% by weight of the formulation;

the formulation is in the form of a matrix tablet which comprises a granulated drug mixed together with the modified release material.

12. The method of claim 11, wherein the tranexamic acid or pharmaceutically acceptable salt thereof is tranexamic acid.