Controlled Release Delivery System for Nasal Applications and Method of Treatment

Abstract

This invention relates to a gel formulation for nasal administration of a controlled release formulation of hormones to the systemic circulation and/or to the brain. The special lipophilic or partly lipophilic system of the invention leads to higher bioavailability of the active ingredient caused by sustained serum levels in plasma but also leads to a more favorable serum level profile. The special lipophilic or partly lipophilic system also allows for the modulation of brain functioning. The invention also relates to the nasal administration of steroid hormones for treatment of female sexual dysfunction (FSD) or female arousal disorder.

1 . A formulation for nasal application comprising: 
 a) at least one hormone drug;    b) at least one lipophilic or partly lipophilic carrier; and    c) at least one compound having surface tension decreasing activity, an amount effective for in situ generation of an emulsion upon contact of the formulation with water.    
   
   
       2 . The formulation according to  claim 1 , wherein the lipophilic carrier comprises an oil.  
   
   
       3 . The formulation according to  claim 2 , wherein the oil is a vegetable oil.  
   
   
       4 . The formulation according to  claim 3 , wherein the vegetable oil is castor oil.  
   
   
       5 . The formulation according to  claim 2 , wherein the amount of oil comprises between 30% and 98% by weight.  
   
   
       6 . The formulation according to  claim 2 , wherein the amount of oil comprises between about 60 to about 98% by weight.  
   
   
       7 . The formulation according to  claim 2 , wherein the amount of oil comprises between about 75% to about 95% by weight.  
   
   
       8 . The formulation according to  claim 2 , wherein the amount of oil comprises between about 85% to about 95% by weight.  
   
   
       9 . The formulation according to  claim 2 , wherein the amount of oil comprises about 90% by weight of the formulation.  
   
   
       10 . The formulation according to  claim 1 , wherein the at least one compound having surface tension decreasing activity comprises at least one surfactant selected from the group consisting of lecithin, fatty acid ester of polyvalent alcohols, of sorbitanes, of polyoxyethylensorbitans, of polyoxyethylene, of sucrose, of polyglycerol and/or at least one humectant selected from the group consisting of sorbitol, glycerine, polyethylene glycol, and macrogol glycerol fatty acid ester, or a mixture thereof.  
   
   
       11 . The formulation according to  claim 10 , wherein the at least one compound having surface tension decreasing activity comprises an oleoyl macrogolglyceride or a mixture of oleoyl macrogolglycerides.  
   
   
       12 . The formulation according to  claim 1 , wherein the at least one compound having surface tension decreasing activity is comprised within the formulation in an amount of from about 1 to about 20% by weight.  
   
   
       13 . The formulation according to  claim 1 , wherein the at least one compound having surface tension decreasing activity is comprised within the formulation in an amount of from about 1 to about 10% by weight.  
   
   
       14 . The formulation according to  claim 1 , wherein the at least one compound having surface tension decreasing activity is comprised within the formulation in an amount of from about 1 to about 5% by weight.  
   
   
       15 . The formulation according to  claim 1 , wherein the at least one compound having surface tension decreasing activity is comprised within the formulation in an amount of about 4% by weight.  
   
   
       16 . The formulation according to  claim 1  further comprising a viscosity regulating agent.  
   
   
       17 . The formulation according to  claim 16 , wherein said viscosity regulating agent comprises a thickener or gelling agent selected from the group consisting of cellulose and cellulose derivatives, polysaccharides, carbomers, polyvinyl alcohol, povidone, colloidal silicon dioxide, cetyl alcohols, stearic acid, beeswax, petrolatum, triglycerides and lanolin, or a mixture thereof.  
   
   
       18 . The formulation according to  claim 17 , wherein said viscosity increasing agent is colloidal silicon dioxide.  
   
   
       19 . The formulation according to  claim 16 , wherein the viscosity regulating agent is comprised within the formulation in an amount of from about 0.5 to about 10% by weight.  
   
   
       20 . The formulation according to  claim 16 , wherein the viscosity regulating agent is comprised within the formulation in an amount of from about 0.5 to about 7% by weight.  
   
   
       21 . The formulation according to  claim 16 , wherein the viscosity regulating agent is comprised within the formulation in an amount of from about 1 to about 4% by weight.  
   
   
       22 . The formulation according to  claim 16 , wherein the viscosity regulating agent is comprised within the formulation in an amount of about 4% by weight.  
   
   
       23 . The formulation according to  claim 1 , wherein the hormone drug is a sexual hormone drug.  
   
   
       24 . The formulation according to  claim 23 , wherein the sexual hormone drug is comprised within the formulation in an amount of from about 0.2 to about 6% by weight.  
   
   
       25 . The formulation according to  claim 23 , wherein the sexual hormone drug is comprised within the formulation in an amount of from about 0.2 to about 4% by weight.  
   
   
       26 . The formulation according to  claim 23 , wherein the sexual hormone drug is testosterone.  
   
   
       27 . A method for the treatment of Female Sexual Dysfunction (FSD) comprising the step of nasally administering to a patient in need of such treatment an effective amount of a formulation comprising: a) at least one sexual hormone drug; b) at least one lipophilic or partly lipophilic carrier; and c) a compound or a mixture of compounds having surface tension decreasing activity, an amount effective for in situ generation of an emulsion upon contact of the formulation with water.  
   
   
       28 . The method according to  claim 27 , wherein the sexual hormone drug is testosterone.  
   
   
       29 . The method according to  claim 27 , wherein the sexual hormone drug is comprised within the formulation in an amount of from about 0.2 to about 6% by weight.  
   
   
       30 . The method according to  claim 27 , wherein the sexual hormone drug is comprised within the formulation in an amount of from about 0.2 to about 4% by weight.  
   
   
       31 . The method according to  claim 27 , wherein the amount of oil comprises between 30% and 98% by weight.  
   
   
       32 . The method according to  claim 27 , wherein the at least one compound having surface tension decreasing activity is comprised within the formulation in an amount of from about 1 to about 20% by weight.  
   
   
       33 . The method according to  claim 27  wherein the formulation further comprises a viscosity regulating agent, wherein the viscosity regulating agent is comprised within the formulation in an amount of from about 0.5 to about 10% by weight.  
   
   
       34 . A method for the treatment of female arousal disorder comprising the step of nasally administering to a patient in need of such treatment an effective amount of a formulation comprising: a) at least one sexual hormone drug; b) at least one lipophilic or partly lipophilic carrier; and c) a compound or a mixture of compounds having surface tension decreasing activity, an amount effective for in situ generation of an emulsion upon contact of the formulation with water.  
   
   
       35 . The method according to  claim 34 , wherein the sexual hormone drug is testosterone.  
   
   
       36 . The method according to  claim 34 , wherein the sexual hormone drug is comprised within the formulation in an amount of from about 0.2 to about 6% by weight.  
   
   
       37 . The formulation according to  claim 34 , wherein the sexual hormone drug is comprised within the formulation in an amount of from about 0.2 to about 4% by weight.  
   
   
       38 . The method according to  claim 34 , wherein the amount of oil comprises between 30% and 98% by weight.  
   
   
       39 . The method according to  claim 34 , wherein the at least one compound having surface tension decreasing activity is comprised within the formulation in an amount of from about 1 to about 20% by weight.  
   
   
       40 . The method according to  claim 34 , wherein the formulation further comprises a viscosity regulating agent, wherein the viscosity regulating agent is comprised within the formulation in an amount of from about 0.5 to about 10% by weight.  
   
   
       41 . A method of increasing an amygdala response in women comprising the step of nasally administering to a woman an effective amount of a formulation comprising: a) at least one sexual hormone drug; b) at least one lipophilic or partly lipophilic carrier; and c) a compound or a mixture of compounds having surface tension decreasing activity, an amount effective for in situ generation of an emulsion upon contact of the formulation with water, 
 wherein the increased amygdala response is associated with the treatment of Female Sexual Dysfunction.    
   
   
       42 . The method according to  claim 41 , wherein the sexual hormone drug is testosterone.  
   
   
       43 . The method according to  claim 41 , wherein the sexual hormone drug is comprised within the formulation in an amount of from about 0.2 to about 6% by weight.  
   
   
       44 . The formulation according to  claim 41 , wherein the sexual hormone drug is comprised within the formulation in an amount of from about 0.2 to about 4% by weight.  
   
   
       45 . The method according to  claim 41 , wherein the amount of oil comprises between 30% and 98% by weight.  
   
   
       46 . The method according to  claim 41 , wherein the at least one compound having surface tension decreasing activity is comprised within the formulation in an amount of from about 1 to about 20% by weight.  
   
   
       47 . The method according to  claim 41 , wherein the formulation further comprises a viscosity regulating agent, wherein the viscosity regulating agent is comprised within the formulation in an amount of from about 0.5 to about 10% by weight.