THERAPEUTIC COMPOSITIONS FOR INTRANASAL ADMINISTRATION OF KETOROLAC

• US 20090042968A1
• Filed: 12/15/2005
• Published: 02/12/2009
• Est. Priority Date: 12/23/2004
• Status: Abandoned Application

• Current Assignee: Egalet US Incorporated (Assertio Holdings, Inc.)
• Original Assignee: ROXRO Pharma, Inc. (Daiichi Sankyo Company Limited)
• Inventors: Thirucote, Ramachandran, Whiting, Roger
• Application Number:
  US11/813,763
• Publication Number:
  US 20090042968A1
• Time in Patent Office: Days
• US Class Current: 514/413
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/167 having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
• CPC Class Codes: A61K 31/407 condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine
• CPC Class Codes: A61K 9/0043 Nose
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/06 Antimigraine agents
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]

Abstract

Therapeutic compositions, particularly sprayable aqueous compositions, comprise ketorolac or a pharmaceutically acceptable salt, in combination with a local anesthetic, such as lidocaine hydrochloride. The compositions are nasally administered to a subject in need thereof to treat pain or inflammation and have the benefit of reduced stinging and improved efficacy, compared to known nasally administered compositions.

Claims

1. A composition for nasal administration to a patient, the composition comprises a therapeutically effective amount of a compound 5-benzoyl-2,3-dihydro-1H-pyrrolizine-1-carboxylic acid, of a formula

an optically active form thereof, a racemic mixture, or a pharmaceutically acceptable salt thereof, in combination with a pharmaceutically acceptable diluent and about 5 to 6% w/v of lidocaine, or a pharmaceutically acceptable salt thereof.

2. The composition of claim 1, wherein the pharmaceutically acceptable salt of the compound is ketorolac tromethamine as a racemic mixture.

3. The composition of claim 1, wherein the composition comprises 25 mg-225 mg of said compound dissolved per mL, wherein the diluent is water and the composition is liquid and sprayable.

4. The composition of claim 3, wherein the composition comprises 50-200 mg of said compound per mL.

5. The composition of claim 1, wherein a chelator is present.

6. The composition of claim 1, wherein the composition comprises about 2.5-22.5% w/v of said compound dissolved in the diluent, which is water.

7. The composition of claim 6, wherein the composition comprises about 15% w/v of said compound.

8. The composition of claim 1, wherein the composition is in a single-dose form for administration to a single patient, wherein the composition is a sprayable liquid and the diluent is water.

9. The composition of claim 1, wherein the composition is in a multi-dose formulation, wherein the composition is a sprayable liquid and the diluent is water.

10. The composition of claim 1, wherein the composition is in a form of an aqueous solution.

11. The composition of claim 1, wherein said pharmaceutically acceptable salt of lidocaine is lidocaine hydrochloride.

14. The composition of claim 1, wherein said composition is contained in a vessel equipped with a device for spraying the composition into the nasal passage of a subject, wherein the composition is an aqueous solution.

15. The composition of claim 14, wherein the vessel holds about 50 to 2000 microliters (μ

L).

16. The composition of claim 1, wherein the pH of the composition is about 6 to 7.5.

18. The composition of claim 1, wherein

(1) water is the sole diluent,

(2) the compound is racemic ketorolac tromethamine dissolved at about 2.5-22.5% w/v,

(3) pharmaceutically acceptable salt of lidocaine is lidocaine hydrochloride dissolved at about 5-6% w/v, and

(4) the pH of the composition is adjusted to 7.2 and a chelator is present.

19. The composition of claim 18, wherein the compound is present at a level of about 15% w/v, potassium phosphate is a pH buffer, and the chelator is sodium EDTA.

20. A method for treating pain or inflammation in a subject in need of such treatment, which comprises intranasally administering to the subject the composition of claim 1.

21. The method of claim 20, wherein the method is for treating pain.

22. The method of claim 21, wherein the pain is the a result of a trauma inflicted on the subject.

23. The method of claim 21, wherein the pain is a result of a medical operation performed on the subject.

24. The method of claim 21, wherein the pain is pathological.

25. The method of claim 21, wherein the pain is neuropathic.

26. The method of claim 21, wherein the pain is migraine or other headache pain.

12. (canceled)

13. (canceled)

17. (canceled)

27-29. -29. (canceled)

30. A composition, wherein

(1) water is a sole diluent,

(2) a racemic ketorolac tromethamine dissolved at about 15% w/v,

(3) a lidocaine hydrochloride dissolved at about 5-6% w/v,

(4) a pH of the composition buffered to 7.2 using potassium phosphate and

(5) sodium EDTA.