Aqueous suspensions of cyclosporin

Abstract

Compositions that are aqueous suspensions of cyclosporin and contain a cyclosporin (e.g., cyclosporin A), a pharmaceutically acceptable water soluble solvent for the cyclosporin, a dispersing agent, a suspending agent and an aqueous vehicle are disclosed. Methods of producing such compositions, as well as methods of using the compositions to treat ophthalmic disorders are also disclosed.

What is claimed is: 
     
         1 . A method of producing a suspension of cyclosporin comprising mixing a cyclosporin solution into an aqueous mixture to precipitate cyclosporin particles having particle size of 20 μm or less as determined by laser light scattering; wherein the cyclosporin solution comprises cyclosporin that is completely dissolved in polyethylene glycol prior to being mixed with the aqueous mixture; wherein the aqueous mixture comprises a dispersing agent, a suspending agent, and an aqueous vehicle; and wherein the suspension of cyclosporin is oil-free and fat free. 
     
     
         2 . The method of  claim 1 , wherein the cyclosporin is cyclosporine. 
     
     
         3 . The method of  claim 1 , wherein the cyclosporin is about 0.005 to about 1.0% w/v of the suspension of cyclosporin. 
     
     
         4 . The method of  claim 1 , wherein the dispersing agent is a surfactant. 
     
     
         5 . The method of  claim 4 , wherein the surfactant is polysorbate 80. 
     
     
         6 . The method of  claim 4 , wherein the surfactant is polysorbate 60. 
     
     
         7 . The method of  claim 4 , wherein the surfactant is polysorbate 40. 
     
     
         8 . The method of  claim 4 , wherein the surfactant is polysorbate 20. 
     
     
         9 . The method of  claim 4 , wherein the surfactant is polyoxyl 40 stearate. 
     
     
         10 . The method of  claim 4 , wherein the surfactant is polyoxyl 15 hydroxystearate. 
     
     
         11 . The method of  claim 4 , wherein the surfactant is a poloxamer. 
     
     
         12 . The method of  claim 4 , wherein the surfactant is tyloxapol. 
     
     
         13 . The method of  claim 4 , wherein the surfactant is POE 35 castor oil. 
     
     
         14 . The method of  claim 1 , wherein the surfactant is a hydrophilic surfactant. 
     
     
         15 . The method of  claim 1 , wherein the suspending agent is carbomer homopolymer, carbomer copolymer, carbomer interpolymer, polycarbophil, a soluble cellulose derivative, polyvinyl alcohol, polyvinypyrrolidone, hyaluronic acid, chondroitin sulfate, gellan, a natural natural gum, a salt thereof, or a combination thereof. 
     
     
         16 . The method of  claim 1 , wherein the suspension of cyclosporin comprises cyclosporin particles of 5 μm or less. 
     
     
         17 . The method of  claim 1 , wherein the cyclosporin particles are amorphous.