TRANEXAMIC ACID FORMULATIONS

• US 20090209646A1
• Filed: 04/30/2009
• Published: 08/20/2009
• Est. Priority Date: 03/04/2004
• Status: Active Grant

• Current Assignee: Amring Pharmaceuticals, Inc.
• Original Assignee: Xanodyne Pharmaceuticals, Inc.
• Inventors: Moore, Keith A., Facemire, John W., Greiwe, Jeffrey S., Modest, Jason D., Heasley, Ralph A.
• Granted Patent: US 8,022,106 B2
• Time in Patent Office: Days
• US Class Current: 514/561
• 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 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 9/2077 Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
• CPC Class Codes: A61P 1/08 for nausea, cinetosis or vertigo; Antiemetics
• 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 modified release oral dosage form comprising tranexamic acid or pharmaceutically acceptable salt thereof and a modified release material which provides for the modified release of the tranexamic acid or pharmaceutically acceptable salt thereof from the dosage form such that the dosage form is suitable for administration on a two or three times a day basis;

said dosage form providing 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 70% by weight tranexamic acid or pharmaceutically acceptable salt thereof released at about 45 minutes and about 100% by weight of said tranexamic acid or pharmaceutically acceptable salt thereof released by about 120 minutes.

2. The modified release oral dosage form of claim 1, wherein said dosage form 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 tranexamic acid or pharmaceutically acceptable salt thereof released at about 15 minutes, from about 20% to about 60% by weight tranexamic acid or pharmaceutically acceptable salt thereof released at about 30 minutes, from about 40% to about 65% by weight tranexamic acid or pharmaceutically acceptable salt thereof released at about 45 minutes, from about 50% to about 95% by weight tranexamic acid or pharmaceutically acceptable salt thereof released at about 60 minutes, and not less than about 60% by weight tranexamic acid or pharmaceutically acceptable salt thereof released at about 90 minutes.

3. The modified release oral dosage form of claim 1, wherein the dosage form releases about 10% to about 25% by weight 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 modified release oral dosage form of claim 1, wherein the dosage form releases about 1% 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 modified release oral dosage form of claim 1 which provides a mean maximum plasma concentration (C_max) of tranexamic acid of from about 9 to about 14.5 mcg/ml after single dose oral administration of about 1300 mg of tranexamic acid or pharmaceutically acceptable salt thereof included in one or more of said modified release oral dosage form to humans.

6. The modified release oral dosage form of claim 1 which provides a mean maximum plasma concentration (C_max) of tranexamic acid of from about 5 to about 25 mcg/ml after steady state oral administration of about 1300 mg of tranexainic acid or pharmaceutically acceptable salt thereof included in one or more of said modified release oral dosage form to humans.

7. The modified release oral dosage form of claim 1 which provides a mean maximum plasma concentration (C_max) of tranexamic acid of from about 10 to about 20 mcg/ml after steady state oral administration of about 1300 mg of tranexamic acid or pharmaceutically acceptable salt thereof included in one or more of said modified release oral dosage form to humans.

8. The modified release oral dosage form of claim 1 which provides mean time to maximum plasma concentration (T_max) at from about 1.0 to about 5.5 hours after oral administration of one or more of said modified release oral dosage form to humans.

9. The modified release oral dosage form of claim 1, wherein the dosage form provides a mean transit time of said tranexamic acid of 7.70±

0.72 hours when orally administered across a patient population.

10. The modified release oral dosage form of claim 1, wherein the dosage form provides a mean absorption time of said tranexamic acid of 4.18±

0.70 hours when orally administered across a patient population.

11. The modified release oral dosage form of claim 1, which provides for the reduction of at least one side effect selected from the group consisting of headache, nausea, vomiting, diarrhea, constipation, cramping, bloating, and combinations thereof, as compared to an immediate release oral dosage form containing an equivalent amount of tranexamic acid or pharmaceutically acceptable salt thereof, when administered across a same or different population of patients as said modified release dosage form, and wherein said immediate release dosage form releases all of said tranexamic acid or pharmaceutically acceptable salt thereof within about 45 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.

12. The modified release oral dosage form of claim 1, which provides a mean transit time of said tranexamic acid which is at least about 20 minutes longer than the immediate release formulation when administered across a patient population.

13. The modified release oral dosage form of claim 1, which provides a mean absorption time of said tranexamic acid which is at least about 20 minutes longer than the immediate release formulation when administered across a patient population.

14. The modified release oral dosage form of claim 1, wherein said dosage form provides less headache, nausea, or combination thereof in comparision to a therapeutically equivalent amount of tranexamic acid or pharmaceutically acceptable salt thereof administered intravenously in five minutes or less when administered across a patient population.

15. The modified release oral dosage form of claim 1, wherein said tranexamic acid or pharmaceutically acceptable salt thereof is included in said dosage form in an amount of from about 375 mg to about 1 gram.

16. The modified release oral dosage form of claim 1, wherein said tranexamic acid or pharmaceutically acceptable salt thereof is included in said dosage form in an amount of about 650 mg.

17. The modified release oral dosage form of claim 1, wherein said dosage form is selected from the group consisting of one or more tablets, capsules, granules, powders, pellets, dragees, troches, non-pareils, and pills.

18. The modified release oral dosage form of claim 1, wherein said dosage form provides a bioavailability of said tranexamic acid of greater than 40% when administered to humans.