Two part formulation system for opthalmic 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 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;   wherein the ophthalmically acceptable liquid comprises a therapeutic amount of the therapeutically active agent.   
     
     
         2 . The product of  claim 1 , wherein the therapeutically active agent comprises phentolamine or a salt thereof. 
     
     
         3 . The product of  claim 1 , wherein the therapeutically active agent comprises a cyclosporine. 
     
     
         4 . The product of  claim 1 , wherein the therapeutically active agent testosterone or a derivative thereof. 
     
     
         5 . The product of  claim 1 , wherein the therapeutically active agent comprises: 
       
         
           
           
               
               
           
         
       
     
     
         6 . The product of  claim 1 , wherein the therapeutically active agent comprises: 
       
         
           
           
               
               
           
         
       
     
     
         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 BAK 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, sorbitan monostearate, polyoxyethylenglyceroltriricinoleate 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 solublilizer, 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 system 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.   
     
     
         17 . The method of  claim 16 , wherein the therapeutically active agent comprises phentolamine or a salt thereof. 
     
     
         18 . The method of  claim 16 , wherein the therapeutically active agent comprises a cyclosporine. 
     
     
         19 . The method of  claim 16 , wherein the therapeutically active agent comprises: 
       
         
           
           
               
               
           
         
       
     
     
         20 . The method of  claim 16 , wherein the therapeutically active agent comprises: