Claims for Patent: 7,915,243

Summary for Patent: 7,915,243

Title:	Topical skin care composition
Abstract:	A cream base for the topical application of skin care therapeutics and a process for making the cream base. In one embodiment, the therapeutic is tretinoin, hydroquinone and fluocinolone acetonide for the treatment of hyperpigmented skin conditions, such as melasma.
Inventor(s):	Puglia; Nancy (Sanford, FL), Ramirez; Rosario (Sanford, FL), Roth; Jerry (Sanford, FL)
Assignee:	Galderma S.A. (Cham, CH)
Application Number:	11/011,176
Patent Claims:	1. A medicated composition for topical application, comprising active ingredients consisting of fluocinolone acetonide, hydroquinone, and tretinoin, wherein the composition is a cream made by a process comprising the steps of: (a) mixing water and at least one hydrophilic compound to form an aqueous phase; (b) mixing at least two hydrophobic compounds to form a non-aqueous phase; (c) mixing the aqueous phase and non-aqueous phase to form a biphasic mixture, wherein steps (a) through (c) are conducted in the absence of an emulsifier; (d) mixing fluocinolone acetonide and tretinoin into the biphasic mixture of step (c); (e) adding at least one emulsifier after step (c) into the biphasic mixture of step (c), or during step (d); and (f) homogenizing the mixture to form an emulsion; wherein hydroquinone is added after adding the at least one emulsifier; and wherein the composition has higher viscosity than a composition made by a process differing only by the addition of an emulsifier to an aqueous or non-aqueous phase prior to mixing the phases. 2. The composition of claim 1, wherein the aqueous phase comprises water, magnesium aluminum silicate, and butylated hydroxytoluene. 3. The composition of claim 1, wherein the non-aqueous phase comprises at least two hydrophobic compounds selected from the group consisting of cetyl alcohol, stearic acid, stearyl alcohol, methyl gluceth, methylparaben, propylparaben, and glycerin. 4. The composition of claim 1, wherein the non-aqueous phase comprises cetyl alcohol, stearic acid, stearyl alcohol, methyl gluceth, methylparaben, propylparaben, and glycerin. 5. The composition of claim 1, wherein the emulsifier is glyceryl stearate, polyethylene glycol (PEG) stearate, or a combination thereof. 6. The composition of claim 1, wherein the emulsifier is a combination of glyceryl stearate and polyethylene glycol stearate. 7. The composition of claim 1, made by a process further comprising the step, following the addition of the emulsifier in step (e), of stirring and cooling the biphasic mixture to about 55.degree. C., then adding hydroquinone. 8. The composition of claim 1, wherein the biphasic mixture is homogenized when the temperature of the mixture is about 50.degree. C. 9. The composition of claim 1, further comprising the step of: (g) stirring and cooling the biphasic mixture to about 45.degree. C., then adding sodium metabisulfite. 10. The composition of claim 1, wherein the active ingredients consist of about 0.01% fluocinolone acetonide, about 4% hydroquinone, and about 0.05% tretinoin, based on the total weight of the composition. 11. The composition of claim 1, wherein the emulsion comprises active ingredients consisting of 0.01 weight % fluocinolone acetonide, 4 weight % hydroquinone, and 0.05 weight % tretinoin; and further comprises 0.04 weight % butylated hydroxytoluene; 4 weight % cetyl alcohol; 0.05 weight % citric acid; 4 weight % glycerin; 3 weight % magnesium aluminum silicate; 5 weight % methyl gluceth; 0.18 weight % methylparaben; 3.5 weight % glyceryl stearate, polyethylene glycol (PEG) stearate or a combination thereof, 0.02 weight % propylparaben, 0.2 weight % sodium metabisulfite, 3 weight % stearic acid, and 4 weight % stearyl alcohol, based on the total weight of the composition. 12. A pharmaceutical composition, comprising active ingredients consisting of 0.01 weight % fluocinolone acetonide, 4 weight % hydroquinone, and 0.05 weight % tretinoin; and further comprising 0.04 weight % butylated hydroxytoluene; 4 weight % cetyl alcohol; 0.05 weight % citric acid; 4 weight % glycerin; 3 weight % magnesium aluminum silicate; 5 weight % methyl gluceth; 0.18 weight % methylparaben; 3.5 weight % glyceryl stearate, polyethylene glycol (PEG) stearate or a combination thereof, 0.02 weight % propylparaben, 0.2 weight % sodium metabisulfite, 3 weight % stearic acid, and 4 weight % stearyl alcohol, based on the total weight of the composition. 13. The composition of claim 1, wherein the emulsion comprises at least one inactive ingredient selected from butylated hydroxytoluene, cetyl alcohol, citric acid, glycerin, glyceryl stearate, magnesium aluminum silicate, methyl gluceth, methylparaben, polyethylene glycol (PEG-100) stearate, propylparaben, purified water, sodium metabisulfite, stearic acid, and stearyl alcohol. 14. The composition of claim 13, wherein the at least one emulsifier is added during step (d). 15. The composition of claim 14, further comprising adding sodium metabisulfite after adding the at least one emulsifier and before adding the hydroquinone. 16. The composition of claim 1, wherein the aqueous and the non-aqueous phases are each mixed at an elevated temperature within the range from about 75.degree. C. to about 80.degree. C. 17. The composition of claim 1, wherein the mixture of step (c) is cooled before adding the active ingredients in step (d). 18. The composition of claim 17, wherein the hydroquinone is added in step (d) following cooling of the mixture. 19. The composition of claim 17, wherein the homogenizing step (f) occurs at a temperature of about 50.degree. C. 20. A medicated composition for topical application, comprising active ingredients consisting of fluocinolone acetonide, hydroquinone, and tretinoin, wherein the active ingredients are effective to treat or alleviate symptoms of hyperpigmented skin conditions, wherein the composition is a cream made by a process comprising the steps of: (a) mixing water and at least one hydrophilic compound to form an aqueous phase; (b) mixing at least two hydrophobic compounds to form a non-aqueous phase; (c) mixing the aqueous and non-aqueous phases to form a biphasic mixture, wherein steps (a) through (c) are conducted in the absence of an emulsifier; (d) mixing fluocinolone acetonide and tretinoin into the mixture of step (c); (e) mixing at least one emulsifier into the mixture of step (d); (f) mixing hydroquinone into the mixture of step (e); and (g) homogenizing the mixture of step (1) to form the emulsion; wherein the composition has higher viscosity than a composition made by a process differing only by the addition of an emulsifier to an aqueous or non-aqueous phase prior to mixing the phases. 21. A homogenous medicated composition in the form of a cream, comprising active ingredients consisting of fluocinolone acetonide, hydroquinone, and tretinoin, wherein the active ingredients are effective to treat or alleviate symptoms of hyperpigmented skin conditions, and further comprising magnesium aluminum silicate, butylated hydroxytoluene, cetyl alcohol, stearic acid, stearyl alcohol, methylparaben, propylparaben, glycerol stearate, polyethylene glycol stearate, glycerol monostearate, or a combination thereof, methyl gluceth, glycerin, citric acid, and sodium metabisulfite; wherein the composition has higher viscosity than a composition made by a process in which an emulsifier is added to an aqueous or non-aqueous phase prior to mixing the phases. 22. The composition of claim 21, comprising active ingredients consisting of about 0.01 wt % fluocinolone acetonide, about 4 wt % hydroquinone, and about 0.05 wt % tretinoin; and further comprising about 3 wt % magnesium aluminum silicate; about 0.04 wt % butylated hydroxytoluene; about 4 wt % cetyl alcohol; about 3 wt % stearic acid; about 4 wt % stearyl alcohol; about 0.18 wt % methylparaben; about 0.02 wt % propylparaben; about 3.5 wt % glycerol stearate, polyethylene glycol stearate, glycerol monostearate, or a combination thereof; about 5 wt % methyl gluceth; about 4 wt % glycerin; about 0.05 wt % citric acid; and about 0.2 wt % sodium metabisulfite, based on the total weight of the composition. 23. The composition of claim 21 in the form of an oil-in-water emulsion.