Brimonidiine gel compositions and methods of use

Abstract

Improved topical gel compositions, such as those containing brimonidine, for the treatment of skin disorders are described. The gel compositions contain carbomer and methylparaben, and are substantially free of methylparaben crystalline particles after an extended period of storage.

1 . A topical gel composition, comprising:
 0.05 to 0.20% (w/w) methylparaben;   one or more second preservatives;   0.80 to 1.50% (w/w) a carbomer;   9.0 to 13.0% (w/w) total polyol,   wherein the topical gel composition has a pH of 4.5 to 7.5, and
 wherein when the concentration of methylparaben is greater than 0.15% (w/w), the concentration of carbomer is less than 1.25% (w/w). 
   
     
     
         2 . The topical gel composition of  claim 1 , wherein the total polyol comprises about 4.5% to 6.5% (w/w) a first polyol. 
     
     
         3 . The topical gel composition of  claim 1 , wherein the gel composition further comprises an alpha adrenergic receptor agonist. 
     
     
         4 . The topical gel composition of  claim 3 , wherein the alpha adrenergic receptor agonist is an alpha-1 or alpha-2 adrenergic receptor agonist. 
     
     
         5 . The topical gel composition of  claim 4 , wherein the alpha adrenergic receptor agonist is selected from the group consisting of oxymetazoline, phenylephrine, methoxyamine, brimonidine, tetrahydrozaline, naphazoline, xylometazoline, epinephrine, and norepinephrine. 
     
     
         6 . A topical gel composition, comprising:
 0.05 to 5% (w/w) brimonidine;   0.05 to 0.20% (w/w) methylparaben;   one or more second preservatives;   0.80 to 1.50% (w/w) a carbomer;   9.0% to 13.0% (w/w) total polyol,   wherein the topical gel composition has a pH of 4.5 to 7.5, and   wherein when the concentration of methylparaben is greater than 0.15% (w/w), the concentration of carbomer is less than 1.25% (w/w)   
     
     
         7 . The topical gel composition of  claim 6 , wherein the total polyol comprises about 4.5% to 6.5% (w/w) a first polyol. 
     
     
         8 . The topical gel composition of  claim 6 , further comprising 0.04 to 0.08% (w/w) water dispersible form of titanium dioxide. 
     
     
         9 . The topical gel composition of  claim 6 , wherein the carbomer is selected from the group consisting of carbomer 934P, Carbopol® 974P, and Carbopol® 980. 
     
     
         10 . The topical gel composition of  claim 6 , wherein the brimonidine is brimonidine tartrate. 
     
     
         11 . The topical gel composition of  claim 6 , wherein the one or more second preservatives are selected from the group consisting of sodium benzoate, phenoxyethanol, benzyl alcohol, imidazolidinyl urea and diazolidinyl urea. 
     
     
         12 . A topical gel composition, comprising:
 0.1 to 0.6% (w/w) brimonidine tartrate;   0.05 to 0.15% (w/w) methylparaben;   one or more second preservatives selected from the group consisting of sodium benzoate, phenoxyethanol, benzyl alcohol, imidazolidinyl urea and diazolidinyl urea;   0.80 to 1.50% (w/w) carbomer;   4.5 to 6.5% (w/w) propylene glycol;   4.5 to 6.5% (w/w) glycerol; and   purified water   wherein the pH of the topical gel composition is adjusted to 5.0 to 6.5 by an adequate amount of sodium hydroxide aqueous solution.   
     
     
         13 . The topical gel composition of  claim 12 , comprising greater than 0.3 (w/w) phenoxyethanol as the second preservative. 
     
     
         14 . The topical gel composition of  claim 13 , further comprising 0.04 to 0.08% (w/w) water dispersible form of titanium dioxide. 
     
     
         15 . A method of treating or preventing a skin disorder in a subject, comprising topically administering to a skin area of the subject the topical gel composition of  claim 6 , wherein the skin area is, or is prone to be, affected by the skin disorder. 
     
     
         16 . The method of  claim 15 , wherein the skin disorder is rosacea, erythema of rosacea, telangiectasias, psoriasis, purpura, erythema of acne, ezama, non-rosacae-related inflammations of skin, flushing, skin sagging, creasing and/or wrinkling, or a symptom associated therewith. 
     
     
         17 . A method of treating or preventing a skin disorder in a subject, comprising topically administering to a skin area of the subject the topical gel composition of  claim 12 , wherein the skin area is, or is prone to be, affected by the skin disorder. 
     
     
         18 . The method of  claim 17 , wherein the skin disorder is rosacea, erythema of rosacea, telangiectasias, psoriasis, purpura, erythema of acne, ezama, non-rosacae-related inflammations of skin, flushing, skin sagging, creasing and/or wrinkling, or a symptom associated therewith. 
     
     
         19 . A method of treating or preventing a skin disorder in a subject, comprising topically administering to a skin area of the subject the topical gel composition of  claim 1 , wherein the gel composition further comprises an alpha adrenergic receptor agonist selected from the group consisting of oxymetazoline, phenylephrine, methoxyamine, brimonidine, tetrahydrozaline, naphazoline, xylometazoline, epinephrine, and norepinephrine, and wherein the skin area is, or is prone to be, affected by the skin disorder. 
     
     
         20 . The method of  claim 19 , wherein the skin disorder is rosacea, erythema of rosacea, telangiectasias, psoriasis, purpura, erythema of acne, ezama, non-rosacae-related inflammations of skin, flushing, skin sagging, creasing and/or wrinkling, or a symptom associated therewith.