Two part formulation system for ophthalmic delivery

Abstract

Ophthalmic products and related methods are described herein. These methods include a stabilizing composition comprising a therapeutically active agent which is separated from a liquid vehicle composition by a barrier. The barrier may be removed to allow the two compositions to mix to provide an ophthalmically acceptable liquid comprising the therapeutically active agent.

1 . An ophthalmic pharmaceutical product comprising:
 a stabilizing composition comprising a therapeutically active agent;   a liquid vehicle composition;   a removable barrier;   wherein the removable barrier is in simultaneous contact with the stabilizing composition and the liquid composition and the removable barrier is configured to prevent contact between the stabilizing composition and the liquid vehicle composition; and   wherein the product is configured to allow removal of the barrier;   wherein the product is configured so that removal of the barrier allows mixing of the stabilizing composition and the vehicle composition to provide a sterile ophthalmically acceptable liquid; and   wherein the ophthalmically acceptable liquid comprises a therapeutic amount of the therapeutically active agent; and   
       wherein the therapeutically active agent is selected from the group consisting of phentolamine, cyclosporin, ketorolac, testosterone or a derivative thereof, docosehexaenoic acid, eicosapentaenoic acid, alpha-linolenic acid, 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         2 . The product of  claim 1 , wherein the therapeutically active agent is phentolamine or a salt thereof. 
     
     
         3 . The product of  claim 1 , wherein the therapeutically active agent is a cyclosporine. 
     
     
         4 . The product of  claim 1 , wherein the therapeutically active agent is testosterone or a derivative thereof. 
     
     
         5 . The product of  claim 1 , wherein the therapeutically active agent is: 
       
         
           
           
               
               
           
         
       
     
     
         6 . The product of  claim 1 , wherein the therapeutically active agent is: 
       
         
           
           
               
               
           
         
       
     
     
         7 . The product of  claim 1 , wherein the stabilizing composition comprises polyethylene glycol (15)-hydroxystearate, polyoxyethylene-polyoxypropylene block copolymer, polyoxyethylene 40 stearate, polysorbate 80, sorbitan monostearate, polyoxyethylenglyceroltriricinoleate 35, a cyclodextrin, or a combination thereof. 
     
     
         8 . The product of  claim 1 , wherein the stabilizing composition comprises potassium chloride, mannitol, sodium chloride, or a combination thereof. 
     
     
         9 . The product of  claim 1 , wherein the stabilizing composition comprises a phosphate buffer, a phosphate citrate buffer, NaOH trolamine, a lactate buffer, a borate buffer, a borate citrate buffer, or a combination thereof. 
     
     
         10 . The product of  claim 1 , wherein the stabilizing composition comprises benzalkonium chloride or is non-preserved. 
     
     
         11 . The product of  claim 1 , wherein the stabilizing composition comprises mannitol, lactose, trehalose, or a combination thereof. 
     
     
         12 . The product of  claim 1 , wherein the liquid vehicle composition comprises polyethylene glycol (15)-hydroxystearate, polyoxyethylene-polyoxypropylene block copolymer, polyoxyethylene 40 stearate, polysorbate 80, polyoxyethylenglycerol triricinoleate 35, a cyclodextrin, or a combination thereof. 
     
     
         13 . The product of  claim 1 , wherein the liquid vehicle composition comprises polyethylene glycol (15)-hydroxystearate, polyoxyethylene-polyoxypropylene block copolymer, polyoxyethylene 40 stearate, polysorbate 80, sorbitan monostearate, polyoxyethylenglyceroltriricinoleate 35, a cyclodextrin, or a combination thereof. 
     
     
         14 . The product of  claim 1 , wherein the liquid vehicle composition is non-preserved, or comprises benzalkonium chloride or a stabilized oxychloro complex. 
     
     
         15 . The product of  claim 1 , wherein the liquid vehicle composition is an aqueous liquid with a pH of about 5 to about 8. 
     
     
         16 . A method of stabilizing a therapeutically active agent for use in an ophthalmically acceptable liquid comprising:
 providing a stabilizing system comprising:   a stabilizing composition comprising the therapeutically active agent;   a vehicle composition comprising at least one of: a solubilizer, a surfactant, an osmolality agent, a buffer, and a preservative; and   a removable barrier separating the stabilizing composition from the vehicle composition;   wherein the system is configured so that removal of the barrier allows mixing between the stabilizing composition and the vehicle to provide a sterile ophthalmically acceptable liquid; and   wherein the ophthalmically acceptable liquid comprises about 0.0001% to about 5% therapeutically active agent by weight and   wherein the therapeutically active agent is selected from the group consisting of phentolamine, cyclosporin, ketorolac, testosterone or a derivative thereof, docosehexaenoic acid, eicosapentaenoic acid, alpha-linolenic acid,   
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         17 . The method of  claim 16 , wherein the therapeutically active agent is phentolamine or a salt thereof. 
     
     
         18 . The method of  claim 16 , wherein the therapeutically active agent is a cyclosporine. 
     
     
         19 . The method of  claim 16 , wherein the therapeutically active agent is: 
       
         
           
           
               
               
           
         
       
     
     
         20 . The method of  claim 16 , wherein the therapeutically active agent is: