Controlled release delivery system for nasal application of neurotransmitters

Abstract

This invention relates to a galenical gel formulation for nasal administration of neurotransmitters/neuromodulators such as dopamine, serotonin or pregnenolone and progesterone. The special lipophilic or partly lipophilic system of the invention leads to high bioavailability of the active ingredient in plasma and brain caused by sustained serum levels and/or direct or partly direct transport from nose to the brain.

1 .- 26 . (canceled) 
     
     
         27 . A dopamine gel formulation for nasal administration comprising: (a) dopamine; (b) at least one lipophilic or partly lipophilic carrier; (c) a compound or a mixture of compounds having surface tension decreasing activity; and (d) a viscosity-regulating agent. 
     
     
         28 . The dopamine gel formulation according to  claim 27 , wherein said dopamine is present in an amount of from about 0.01% to about 6% by weight of the dopamine gel formulation. 
     
     
         29 . The dopamine gel formulation according to  claim 27 , wherein said at least one lipophilic or partly lipophilic carrier is present in the dopamine gel formulation in an amount of from about 30% to about 98% by weight of the dopamine gel formulation. 
     
     
         30 . The dopamine gel formulation according to  claim 27 , wherein said at least one lipophilic carrier or partly lipophilic carrier is selected from a group consisting of a fat, oil, wax, cholesterol, sterol, monoglyceride, diglyceride, triglyceride, phospholipid and mixtures thereof. 
     
     
         31 . The dopamine gel formulation according to  claim 30 , wherein said oil is castor oil. 
     
     
         32 . The dopamine gel formulation according to  claim 27 , wherein said compound or mixture of compounds having surface tension decreasing activity is present in an amount of from about 1% to about 20% by weight of the dopamine gel formulation. 
     
     
         33 . The dopamine gel formulation according to  claim 27 , wherein said compound or mixture of compounds having surface tension decreasing activity comprises at least one surfactant selected from the group consisting of lecithin, a fatty acid ester, at least one humectant, and mixtures thereof. 
     
     
         34 . The dopamine gel formulation according to  claim 33 , wherein said compound or mixture of compounds having surface tension decreasing activity comprises an oleoyl macrogolglyceride or mixtures of oleoyl macrogolglycerides. 
     
     
         35 . The dopamine gel formulation according to  claim 27 , wherein said viscosity-regulating agent is present in an amount of from about 0.5% to about 10% by weight of the dopamine gel formulation. 
     
     
         36 . The dopamine gel formulation according to  claim 27 , wherein said viscosity-regulating agent comprises a thickener or gelling agent selected from the group consisting of cellulose, cellulose derivatives, polysaccharides, carbomers, polyvinyl alcohol, povidone, colloidal silicon dioxide, cetyl alcohols, stearic acid, beeswax, petrolatum, triglycerides, lanolin and mixtures thereof. 
     
     
         37 . The dopamine gel formulation according to  claim 36 , wherein said viscosity-regulating agent is colloidal silicon dioxide. 
     
     
         38 . The dopamine gel formulation according to  claim 27 , wherein said dopamine is in the form of microspheres. 
     
     
         39 . The dopamine gel formulation according to  claim 27 , wherein said dopamine is in the form of liposomes. 
     
     
         40 . A dopamine gel formulation comprising: (a) dopamine in an amount of from about 0.01% to about 6% by weight of the formulation; (b) at least one lipophilic or partly lipophilic carrier in an amount of from about 30% to about 98% by weight of the formulation; (c) a compound or a mixture of compounds having surface tension decreasing activity present in an amount of from about 1% to about 20% by weight of the formulation; and (d) a viscosity-regulating agent present in an amount of from about 0.5% to about 10% by weight of the formulation. 
     
     
         41 . A method of providing dopaminergic activity to brain tissue of a subject in need thereof, comprising administering a dopamine gel formulation according to  claim 27  to the nasal mucosa of the subject.