DICLOFENAC GEL

• US 20120295978A1
• Filed: 08/01/2012
• Published: 11/22/2012
• Est. Priority Date: 10/17/2006
• Status: Active Grant

• Current Assignee: Horizon Therapeutics Ireland Dac
• Original Assignee: Nuvo Research AG (Searchlight Pharma, Inc.)
• Inventors: KISAK, Ed, SINGH, Jagat
• Granted Patent: US 8,563,613 B2
• Time in Patent Office: Days
• US Class Current: 514/567
• 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 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 47/18 Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
• CPC Class Codes: A61K 47/183 Amino acids, e.g. glycine, EDTA or aspartame
• CPC Class Codes: A61K 47/20 containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
• CPC Class Codes: A61K 47/32 Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers , poly(meth)acrylates, or polyvinyl pyrrolidone
• CPC Class Codes: A61K 47/34 Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers A61K47/10 takes precedence
• CPC Class Codes: A61K 47/38 Cellulose; Derivatives thereof
• CPC Class Codes: A61K 9/0014 Skin, i.e. galenical aspects of topical compositions non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00
• CPC Class Codes: A61K 9/06 Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels composition of ointments, creams or gels A61K47/00
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]

Abstract

The present invention provides a gel formulation comprising diclofenac sodium which has superior transdermal flux properties, which may be used for the topical treatment of pain, such as in osteoarthritis.

Claims

1. A topical formulation comprising:

(i) 1-5% w/w diclofenac sodium;

(ii) 30-60% w/w DMSO;

(iii) 1-15% w/w propylene glycol;

(iv) 1-30% w/w ethanol;

(v) optionally glycerine;

(vi) water; and

(vii) at least one thickening agent selected from the group consisting of a cellulose polymer, a carbomer polymer, a carbomer derivative, a cellulose derivative, and mixtures thereof.

2. The topical formulation of claim 1, wherein the concentration of diclofenac sodium is a member selected from the group consisting of 1%, 1.5% and 2% w/w, and all fractions in between.

3. The topical formulation of claim 1, wherein the concentration of DMSO is about 40% to about 50% w/w.

4. The topical formulation of claim 3, wherein the concentration of DMSO is a member selected from the group consisting of 40%, 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49% and 50% w/w, and all fractions in between.

5. The topical formulation of claim 1, wherein the concentration of ethanol is present at 23-29% w/w.

6. The topical formulation of claim 1, wherein the at least one thickening agent is selected from the group consisting of a carbomer polymer, a carbomer derivative and mixtures thereof.

7. The topical formulation of claim 6, wherein the at least one thickening agent is selected from the group consisting of carbopol 971, carbopol 981, carbopol 941, carbopol 1342 and ultrez 10.

8. The topical formulation of claim 6, wherein glycerine is present.

9. The topical formulation of claim 1, wherein the at least one thickening agent is selected from the group consisting of a cellulose polymer, a cellulose derivative, and mixtures thereof.

10. The topical formulation of claim 9, wherein the at least one thickening agent is hydroxypropyl cellulose.

11. A topical formulation comprising:

(i) 1-5% w/w diclofenac sodium;

(ii) 40-50% w/w DMSO;

(iii) 23-29% w/w ethanol;

(iv) 10-12% w/w propylene glycol;

(v) hydroxypropyl cellulose; and

(vi) water, wherein the topical formulation has a viscosity of 500-5000 centipoise.

12. The topical formulation of claim 11, wherein the concentration of diclofenac sodium is a member selected from the group consisting of 1%, 1.5% and 2% w/w, and all fractions in between.

13. The topical formulation of claim 11, wherein the concentration of DMSO is a member selected from the group consisting of 40%, 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49% and 50% w/w, and all fractions in between.

14. The topical formulation of claim 11, wherein the concentration of ethanol is present at 26.5% w/w.

15. A method for treating pain in a subject suffering from pain, said method comprising the topical administration of a formulation comprising:

(i) diclofenac sodium present at 1-5% w/w;

(ii) DMSO present at 30-60% w/w;

(iii) ethanol present at 1-30% w/w;

(iv) propylene glycol present at 1-15% w/w;

(v) optionally glycerine;

(vi) a thickening agent, wherein said thickening agent is selected from the group consisting of cellulose polymers, carbomer polymers, a carbomer derivative, a cellulose derivative and mixtures thereof; and

(vii) water.

16. The method of claim 15, wherein the concentration of diclofenac sodium is a member selected from the group consisting of 1%, 1.5% and 2% w/w, and all fractions in between.

17. The method of claim 15, wherein the concentration of DMSO is about 40% to about 50% w/w.

18. The method of claim 17, wherein the concentration of DMSO is a member selected from the group consisting of 40%, 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49% and 50% w/w, and all fractions in between.

19. The method of claim 15, wherein the concentration of ethanol is present at 23-29% w/w.

20. The method of claim 15, wherein the at least one thickening agent is selected from the group consisting of a carbomer polymer, a carbomer derivative and mixtures thereof.

21. The method of claim 20, wherein glycerine is present.

22. The method of claim 15, wherein the at least one thickening agent is selected from the group consisting of a cellulose polymer, a cellulose derivative, and mixtures thereof.

23. The method of claim 22, wherein the at least one thickening agent is hydroxypropyl cellulose.

24. A method for treating signs or symptoms associated with osteoarthritis, said method comprising:

administering a formulation comprising diclofenac sodium present at 2% w/w, wherein the administration of the formulation is twice daily, to thereby effectively treat the signs or symptoms associated with osteoarthritis.

25. The method of claim 24, wherein the formulation further comprises DMSO present at a concentration of 30-60% w/w.

26. The method of claim 25, wherein the concentration of DMSO is a member selected from the group consisting of 40%, 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49% and 50% w/w, and all fractions in between.

27. The method of claim 24, wherein the formulation further comprises ethanol present at a concentration of 23-29% w/w.

28. The method of claim 24, wherein the formulation further comprises at least one thickening agent.

29. The method of claim 28, wherein the at least one thickening agent is hydroxypropyl cellulose.

30. The method of claim 24, wherein the formulation has improved absorption on a per dose basis compared to a comparative liquid composition.