IP Library Granted Patent US 10,471,068
Granted Patent B2
US 10,471,068 · App. 15/976,800 · Granted Nov 12, 2019

Pharmaceutical compositions comprising meloxicam

Inventor: Herriot Tabuteau (New York, NY)
Assignee: AXSOME THERAPEUTICS, INC.
A61K31/5415A61K9/0053A61K9/205A61K9/2009A61K9/209A61K9/2086A61K31/4196A61K47/02A61K47/40A61K47/6951A61P29/00
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Quick Facts
Patent No.
US 10,471,068
App. No.
15/976,800
Granted
Nov 12, 2019
Kind
B2
Abstract

Disclosed herein are compositions comprising a drug such as a triptan (e.g. rizatriptan) and/or an NSAID (e.g. meloxicam) in combination with a cyclodextrin and/or a carbonate or a bicarbonate. These compositions may be orally administered, for example, to improve the bioavailability or pharmacokinetics of the drug for the treatment of conditions such as pain.

Claims (26)

1. A method of dissolving a combination of meloxicam and a rizatriptan in a stomach of a human being, comprising orally administering, to the human being, a solid dosage form comprising: 1) meloxicam, 2) a sulfobutyl ether β-cyclodextrin (SBEβCD), 3) a bicarbonate, and 4) the rizatriptan, wherein the solid dosage form has improved dissolution of meloxicam as compared to a reference solid dosage form containing: 1) the same amount of meloxicam, 2) the same amount of the SBEβCD, and 3) no bicarbonate, wherein the improved dissolution of meloxicam is determined by the following test: adding the solid dosage form or the reference solid dosage form to 500 mL of a 0.01 N HCl aqueous solution, stirring at 75 revolutions per minute (RPM) with a USP paddle apparatus II at 37° C., and determining the amount of meloxicam dissolved in the 0.01 N HCl aqueous solution after 15 minutes.

2. The method of claim 1 , wherein about 8 mg to about 13 mg of the rizatriptan is present in the solid dosage form based upon the weight of the rizatriptan in the free base form.

3. The method of claim 2 , wherein the rizatriptan is present in a salt form in an amount that is a molar equivalent to about 10 mg of the rizatriptan in the free base form.

4. The method of claim 3 , wherein the rizatriptan is present as rizatriptan benzoate.

5. The method of claim 1 , wherein the solid dosage form contains about 15 mg to about 25 mg of meloxicam.

6. The method of claim 5 , wherein the solid dosage form contains about 20 mg of meloxicam.

7. The method of claim 1 , wherein the SBEβCD has about 6 to about 7 sulfobutyl ether groups for each molecule of β-cyclodextrin.

8. The method of claim 1 , wherein the solid dosage form contains about 100 mg to about 175 mg of the SBEβCD.

9. The method of claim 8 , wherein the solid dosage form contains about 100 mg to about 140 mg of the SBEβCD.

10. The method of claim 1 , wherein the bicarbonate comprises sodium bicarbonate.

11. The method of claim 1 , wherein the solid dosage form contains about 400 mg to about 600 mg of the bicarbonate.

12. The method of claim 1 , wherein the solid dosage form contains about 500 mg of sodium bicarbonate.

13. The method of claim 1 , wherein the solid dosage form is orally administered to the human being to treat migraine.

14. A method of dissolving a combination of meloxicam and a rizatriptan in a stomach of a human being, comprising orally administering, to the human being, a solid dosage form comprising: 1) meloxicam, 2) a sulfobutyl ether β-cyclodextrin (SBEβCD), 3) a bicarbonate, and 4) the rizatriptan, wherein the solid dosage form has improved dissolution of meloxicam as compared to a solid reference dosage form containing: 1) the same amount of meloxicam, 2) the same amount of the SBEβCD, and 3) no bicarbonate, wherein the improved dissolution of meloxicam is determined by the following test: adding the solid dosage form or the reference solid dosage form to 500 mL of a 0.01 N HCl aqueous solution, stirring at 75 revolutions per minute (RPM) with a USP paddle apparatus II at 37° C., and determining the amount of meloxicam dissolved in the 0.01 N HCl aqueous solution after 60 minutes.

15. The method of claim 14 , wherein about 8 mg to about 13 mg of the rizatriptan is present in the solid dosage form based upon the weight of the rizatriptan in the free base form.

16. The method of claim 15 , wherein the rizatriptan is present in a salt form in an amount that is a molar equivalent to about 10 mg of the rizatriptan in the free base form.

17. The method of claim 16 , wherein the rizatriptan is present as rizatriptan benzoate.

18. The method of claim 14 , wherein the solid dosage form contains about 15 mg to about 25 mg of meloxicam.

19. The method of claim 18 , wherein the solid dosage form contains about 20 mg of meloxicam.

20. The method of claim 14 , wherein the SBEβCD has about 6 to about 7 sulfobutyl ether groups for each molecule of β-cyclodextrin.

21. The method of claim 14 , wherein the solid dosage form contains about 100 mg to about 175 mg of the SBEβCD.

22. The method of claim 21 , wherein the solid dosage form contains about 100 mg to about 140 mg of the SBEβCD.

23. The method of claim 14 , wherein the bicarbonate comprises sodium bicarbonate.

24. The method of claim 14 , wherein the solid dosage form contains about 400 mg to about 600 mg of the bicarbonate.

25. The method of claim 14 , wherein the solid dosage form contains about 500 mg of sodium bicarbonate.

26. The method of claim 14 , wherein the solid dosage form is orally administered to the human being to treat migraine.

Assignments (4)
RELEASE OF SECURITY INTEREST Recorded May 22, 2025
From: HERCULES CAPITAL, INC.
To: AXSOME THERAPEUTICS, INC.
Reel/Frame 071337/0004 →
SECURITY INTEREST Recorded May 9, 2025
From: AXSOME THERAPEUTICS, INC.; AXSOME MALTA LTD.
To: WILMINGTON TRUST, NATIONAL ASSOCIATION
Reel/Frame 071247/0836 →
INTELLECTUAL PROPERTY SECURITY AGREEMENT Recorded Sep 25, 2020
From: AXSOME THERAPEUTICS, INC.
To: HERCULES CAPITAL, INC., AS AGENT
Reel/Frame 053941/0491 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 21, 2018
From: TABUTEAU, HERRIOT
To: AXSOME THERAPEUTICS, INC.
Reel/Frame 045865/0762 →
Continuity (5)
Continuation In Part PCTUS2018012433 · Jan 4, 2018
Provisional Application 62536466 · Jul 25, 2017
Provisional Application 62504105 · May 10, 2017
Provisional Application 62442136 · Jan 4, 2017
Related Publication 20180256593A1 · Sep 13, 2018
Cited By (16)
US 12,268,693 US 12,357,640 US 12,370,196 US 12,472,255 US 12,472,256 US 12,472,257 US 12,472,258 US 12,478,678 US 12,485,176 US 12,544,383 US 12,551,488 US 12,551,489 US 12,611,413 US 12,616,752 US 12,685,736 US 12,691,123