Topical composition
The invention relates to beneficial topical pharmaceutical compositions comprising the diclofenac sodium salt in unusually low amounts. The compositions represent opaque emulsion-gels, in which diclofenac is kept fully dissolved.
1. A low-dose diclofenac composition in the form of a pharmaceutically acceptable opaque emulsion-gel for topical administration which comprises:
(a) 0.1-0.4% (w/w) of diclofenac sodium salt,
(b) at least 50% (w/w) of water,
(c) 0-30% (w/w of at least one C 2 -C 4 -alkanol,
(d) 3-20% (w/w) of a glycol solvent selected from the group consisting of propylene glycol and polyethylene glycol (200-20000),
(e) 0.2-3% (w/w) of at least one gelling agent selected from the group consisting of carbomers,
(f) 2-8% (w/w) of at least one lipid forming the oily phase of the emulsion-gel,
(g) 1-5% (w/w) of at least one non-ionic surfactant, and
(h) a basic agent selected from the group consisting of ammonia, sodium hydroxide and potassium hydroxide to adjust the pH of the total composition to 6.5-8;
wherein said composition is devoid of an antifungal drug, and is free of added antioxidants or chelating agents.
2. A composition according to claim 1 herein the diclofenac of (a) is the sole pharmaceutically active substance.
3. A composition according to claim 1 which is free of diethanolamine or other neutralizing organic amines.
4. A low-dose diclofenac composition in the form of a pharmaceutically acceptable opaque emulsion-gel for topical administration which comprises:
(a) 0.1-0.4% (w/w) of diclofenac sodium salt,
(b) at least 50% (w/w) of water,
(c) 0-30% (w/W) of at least one C 2 -C 4 -alkanol,
(d) 3-20% (w/w) of a glycol solvent selected from the group consisting of propylene glycol and polyethylene glycol (200-20000).
(e) 0.2-3% (w/w) of at least one gelling agent selected from the group consisting of carbomers,
(f) 2-8% (w/w) of at least one lipid forming the oily phase of the emulsion-gel,
(g) 1-5% (w/w) of at least one non-ionic surfactant, and
(h) a basic agent selected from the group consisting of ammonia, sodium hydroxide and potassium hydroxide to adjust the pH of the total composition to 6.5-8;
wherein (1) said diclofenac of (a) is the sole pharmaceutically active substance in said composition; (2) said composition is free of diethanolamine or other neutralizing organic amines; and (3) said composition is free of added antioxidants or chelating agents.
5. A composition according to claim 4 which comprises
(a) 0.1-0.3% of diclofenac sodium salt,
(b) 60-92% of water,
(c) 0-25% of ethanol, isopropanol, or mixtures thereof,
(d) 3-20% of propylene glycol,
(e) 0.3-2% of at least one gelling agent selected from the group consisting of carbomers,
(f) 3-7% of at least one lipid forming the fatty phase of the emulsion-gel selected from mixtures of paraffin and C 6 -C 12 -alkanoic acid C 12 -C 18 -alkyl esters, and isopropyl myristate and C 6 -C 12 -alkanoic acid C 12 -C 18 -alkyl esters.
(g) 1-3% of at least one non-ionic surfactant, and
(h) ammonia to adjust the pH of the total composition to 6.5-8.
6. A composition according to claim 1 wherein the polyethylene glycol (200-20000) usable as component (d) is selected from polyethylene glycol (200-1000)
7. A composition according to claim 4 wherein the polyethylene glycol (200-20000) usable as component (d) is selected from polyethylene glycol (200-1000).
8. A composition according to claim 1 , which comprises (c) in an amount of from 0 up to 5% and (d) in an amount from 3 up to 7% of total composition.
9. A composition according to claim 4 , which comprises (c) in an amount of from 0 up to 5% and (d) in an amount from 3 up to 7% of total composition.
10. A composition according to claim 1 , which comprises as C 2 -C 4 -alkanol (c) isopropanol.
11. A composition according to claim 4 , which comprises as C 2 -C 4 -alkanol (c) isopropanol.
12. A composition according to claim 1 , which comprises as gelling agent (e) carbomer 980 , carbomer 940 , carbomer 981 , carbomer 941 , carbomer 974 , carbomer 934 , carbomer 910 , or a mixture of any of said carbomers.
13. A composition according to claim 4 , which comprises as gelling agent (e) carbomer 980 , carbomer 940 , carbomer 981 , carbomer 941 , carbomer 974 , carbomer 934 , carbomer 910 , or a mixture of any of said carbomers.
14. A composition according to claim 10 , which comprises as lipid (f) a mixture of either paraffin or isopropyl myristate with C 6 -C 12 -alkanoic acid C 12 -C 18 -alkyl esters.
15. A composition according to claim 11 , which comprises as lipid (f) a mixture of either paraffin or isopropyl myristate with C 6 -C 12 -alkanoic acid C 12 -C 18 -alkyl esters.
16. A composition according to claim 14 , which comprises as non-ionic surfactant (g) a polyoxyethylene (10-30) fatty alcohol ether.
17. A composition according to claim 15 , which comprises as non-ionic surfactant (g) a polyoxyethylene (10-30) fatty alcohol ether.
18. A low-dose diclofenac composition in the form of a pharmaceutically acceptable opaque emulsion-gel for topical administration which comprises:
(a) 0.1% (w/w) of diclofenac sodium
(b) at least 50% (w/w) of water,
(c) 0-30% (w/w) of ethanol, isopropanol, or mixtures thereof,
(d) 3-20% (w/w) of propylene glycol,
(e) 0.2-3% (w/w) of at least one gelling agent selected from the group consisting of carbomers 980 , 940 , 981 , 941 , 974 , 934 and 910 ,
(f) 2-8% (w/w) of a mixture of liquid paraffin or isopropyl myristate with coco-caprylate/caorate,
(g) 1-5% (w/w) of at least one non-ionic surfactant which is a polyoxyethylene (10-30) fatty alcohol ether, and
(h) a basic agent selected from the group consisting of ammonia, sodium hydroxide and potassium hydroxide to adjust the pH of the total composition to 6.5-8;
wherein said composition is devoid of an antifungal drug and is free of added antioxidants or chelating agents.
19. A composition according to claim 18 wherein the diclofenac of (a) is the sole pharmaceutically active substance.
20. A composition according to claim 18 which is free of diethanolamine or other neutralizing organic amines.
21. A composition according to claim 1 which comprises
(a) 0.1-0.3% of diclofenac sodium salt,
(b) 60-92% of water,
(c) 0-25% of ethanol, isopropanol, or mixtures thereof,
(d) 3-20% of propylene glycol,
(e) 0.3-2% of at least one gelling agent selected from the group consisting of carbomers,
(f) 3-7% of at least one lipid forming the fatty phase of the emulsion-gel selected from mixtures of paraffin and C 6 -C 12 -alkanoic acid C 12 -C 18 -alkyl esters, and isopropyl myristate and C 6 -C 12 -alkanoic acid C 12 -C 18 -alkyl esters,
(g) 1-3% of at least one non-ionic surfactant, and
(h) ammonia to adjust the pH of the total composition to 6.5-8.
22. A composition according to claim 1 wherein the emulsion-gel comprises:
(a) 0.1-0.4% (w/w) of diclofenac sodium salt,
(b) at least 50% (w/w) of water,
(c) 0-30% (w/w) of isopropanol,
(d) 3-20% (w/w) of propylene glycol,
(e) 0.2-3% (w/w) of gelling agent selected from carbomers,
(f) 2-8% (w/w) of a mixture of liquid paraffin and coco-caprylate/caprate,
(g) 1-5% (w/w) of polyoxyethylene-20-cetostearyl ether, and
(h) a basic agent selected from the group consisting of ammonia, sodium hydroxide and potassium hydroxide to adjust the pH of the total composition to 6.5-8.
23. A composition according to claim 1 wherein the formulation comprises component (a), diclofenac sodium salt, in an amount of 0.1%.
24. A composition according to claim 4 wherein the formulation comprises component (a), diclofenac sodium salt, in an amount of 0.1%.
25. A composition according to claim 21 wherein the formulation comprises component (a), diclofenac sodium salt, in an amount of 0.1%.
26. A composition according to claim 22 wherein the formulation comprises component (a), diclofenac sodium salt, in an amount of 0.1%.
27. A composition according to claim 23 wherein the diclofenac sodium is 100% stable following 9 months storage under conditions of temperature (°C.) and relative humidity (r.h.) of 25° C./60% r.h. or 30° C./60% t.h.
28. A composition according to claim 24 wherein the diclofenac sodium is 100% stable following 9 months' storage under conditions of temperature (°C.) and relative humidity (r.h.) of 25° C./60% r.h. or 30° C./60% t.h.
29. A composition according to claim 25 wherein the diclofenac sodium is 100% stable following 9 months' storage under conditions of temperature (°C.) and relative humidity (r.h.) of 25° C./60% r.h. or 30° C./60% t.h.
30. A composition according to claim 26 wherein the diclofenac sodium is 100% stable following 9 months' storage under conditions of temperature (°C.) and relative humidity (r.h.) of 25° C./60% r.h. or 30°C./60% t.h.