Ophthalmic emulsion

Abstract

The present invention is directed to an ophthalmic emulsion. The emulsion has a unique combination of ingredients that promotes the stability of small oil droplets within the emulsion. The emulsion also includes a mucoadhesive polymer that aid in delivering a lipid to the ocular surface.

1 . An ophthalmic emulsion, the emulsion comprising:
 water forming an aqueous phase;   oil forming an oil phase;   a hydrophilic surfactant;   a hydrophobic surfactant;   a charged phospholipid;   borate; and   a mucoadhesive galactomannan polymer;   wherein:   i. the oil phase is in droplets within the aqueous phase and the droplets have an average diameter that is no greater than about 1000 nm but is at least 10 nm; and   ii. the borate and galactomannan polymer cooperatively act to form a gel upon instillation of the emulsion in an eye of an individual.   
     
     
         2 . An emulsion as in  claim 1  wherein the oil is a hydrocarbon selected from mineral oil, paraffin oil and petrolatum. 
     
     
         3 . An emulsion as in  claim 1  wherein the oil is at least 0.1 w/v % and no greater than 3 w/v % of the emulsion 
     
     
         4 . An emulsion as in  claim 3  wherein the hydrophilic surfactant is present in the emulsion in an amount that is at least 0.08 w/v % and is no greater than about 0.8 w/v %. 
     
     
         5 . An emulsion as in  claim 4  wherein the hydrophilic surfactant is polyoxyethylene-40-stearate. 
     
     
         6 . An emulsion as in  claim 4  wherein the hydrophobic surfactant is at least about 0.01 w/v % and is no greater than 2.0 w/v %. 
     
     
         7 . An emulsion as in  claim 6  wherein the hydrophobic surfactant is a sorbitan tristearate. 
     
     
         8 . An emulsion as in  claim 1  wherein the mucoadhesive galactomannan polymer is selected from the group consisting of guar and hydroxypropyl guar. 
     
     
         9 . An emulsion as in  claim 8  wherein the mucoadhesive galactomannan polymer is present in the emulsion at a concentration of at least about 0.01 w/v % but no greater than 1.0 w/v %. 
     
     
         10 . An emulsion as in  claim 8  wherein the charged phospholipid is an anionic phospholipid named dimyristoyl phosphatidylglycerol. 
     
     
         11 . An emulsion as  claim 10  wherein the phospholipid is present in the emulsion in a concentration from about 0.05 to 7.0 percent by weight 
     
     
         12 . An emulsion as in  claim 1  further comprising a borate/polyol buffer system. 
     
     
         13 . An emulsion as in  claim 12  further comprising a polymeric quaternary ammonium compound as an anti-microbial preservative. 
     
     
         14 . An ophthalmic emulsion, the emulsion comprising:
 water forming an aqueous phase;   oil forming an oil phase wherein the oil is a hydrocarbon selected from mineral oil, paraffin oil and petrolatum and the oil is at least 0.8 w/v % and is no greater than 1.5 w/v % of the emulsion;   a hydrophilic surfactant present in the emulsion in an amount that is at least about 0.14 w/v % and is no greater than about 0.44 w/v %;   a hydrophobic surfactant present in the emulsion in an amount that is at least about 0.16 w/v % and is no greater than about 0.62 w/v %;   a charged phospholipid wherein the phospholipid is present in the emulsion in a concentration from about 0.05 to 7.0 percent by weight;   borate; and   a mucoadhesive galactomannan polymer wherein the mucoadhesive galactomannan polymer is selected from the group consisting of guar and hydroxypropyl guar and wherein the mucoadhesive galactomannan polymer is present in the emulsion at a concentration of at least about 0.03 w/v %, but no greater than about 0.08 w/v %;   wherein:   i. the oil phase is in droplets within the aqueous phase and the droplets have an average diameter that is no greater than about 500 nm but is at least 100 nm; and   ii. the borate and galactomannan polymer cooperatively act to form a gel upon instillation of the emulsion in an eye of an individual.   
     
     
         15 . An emulsion as in  claim 14  further comprising a borate/polyol buffer system and a polymeric quaternary ammonium compound as an anti-microbial preservative;
 wherein the hydrophilic surfactant is polyoxyethylene-40-stearate and wherein the hydrophobic surfactant is a sorbitan tristearate and wherein the charged phospholipid is an anionic phospholipid named dimyristoyl phosphatidylglycerol. 
 
     
     
         16 . A method of using the emulsion of  claim 1 , comprising:
 instilling the emulsion into an eye of a mammal.   
     
     
         17 . A method of using the emulsion of  claim 14 , comprising:
 instilling the emulsion into an eye of a mammal.   
     
     
         18 . A method as in  claim 16  wherein the mammal is a human being and the emulsion is instilled as drops from an eye dropper. 
     
     
         19 . A method as in  claim 17  wherein the mammal is a human being and the emulsion is instilled as drops from an eye dropper. 
     
     
         20 . A method of forming an emulsion as in  claim 1 , comprising:
 forming a first admixture by mixing the oil and the surfactants at an elevated temperature to form an oil phase admixture;   forming a second admixture by mixing the anionic phospholipid into purified water at an elevated temperature to form a water phase admixture;   mixing the oil phase admixture and the water phase admixture at an elevated temperature and subsequently homogenizing the oil phase mixture with the water phase mixture to form an initial emulsion; and   forming a third admixture by mixing the galactomannan polymer with water and adjusting pH as needed to form a galactomannan polymer slurry; and   mixing the galactomannan polymer slurry with the initial emulsion to form a polymer enhanced emulsion.   
     
     
         21 . A method as in  claim 20  further comprising:
 forming a fourth admixture by mixing any combination of the following to form a salt solution: borate, polyol, preservative and any other ingredients; and 
 mixing the salt solution with the enhanced emulsion followed by the addition of a sufficient quantity (Q.S.) of water and pH adjustment. 
 
     
     
         22 . A method of forming an emulsion as in  claim 14 , comprising:
 forming a first admixture by mixing the oil and the surfactants at an elevated temperature to form an oil phase admixture;   forming a second admixture by mixing the anionic phospholipid into purified water at an elevated temperature to form a water phase admixture;   mixing the oil phase admixture and the water phase admixture at an elevated temperature and subsequently homogenizing the oil phase mixture with the water phase mixture to form an initial emulsion; and   forming a third admixture by mixing the galactomannan polymer with water and adjusting pH as needed to form a galactomannan polymer slurry; and   mixing the galactomannan polymer slurry with the initial emulsion to form a polymer enhanced emulsion.   
     
     
         23 . A method as in  claim 22  further comprising:
 forming a fourth admixture by mixing any combination of the following to form a salt solution: borate, polyol, preservative and any other ingredients; and 
 mixing the salt solution with the enhanced emulsion followed by the addition of a sufficient quantity (Q.S.) of water and pH adjustment.