Cyclosporin a formulations as nanoparticles

Abstract

Cyclosporin A formulations are provided as amorphous nanoparticle dispersions for physiologic absorption.. The compositions have high bioavailability and patient acceptability. By providing for concentrates comprising lower alkanols and a polyoxyalkylene surfactant as a stable dispersion of cyclosporin A, upon introducing the stable dispersion into an aqueous medium, the subject formulation is produced comprising amorphous bioavailable cyclosporin nanoparticles.

What is claimed is:  
     
         1 . An aqueous dispersion of cyclosporin nanoparticles, wherein at least 50 weight percent of the cyclosporin present in the dispersion is of particles less than about 1 μm, said cyclosporin being amorphous.  
     
     
         2 . A dispersion according to  claim 1 , comprising in minor amounts lower alkanol and at least one polyoxyethylene surfactant.  
     
     
         3 . A dispersion according to  claim 2 , wherein said polyoxyethylene surfactant is polysorbate  80 .  
     
     
         4 . A dispersion according to  claim 2 , wherein said lower alkanol is at least one of ethanol and propylene glycol.  
     
     
         5 . A dispersion according to  claim 1 , comprising a polyethylene glycol of less than about 2000 Daltons.  
     
     
         6 . In a method for orally administering cyclosporin to a patient, the improvement which comprises: 
 providing said cyclosporin, wherein at least 50 weight % of said cyclosporin is as amorphous particles of less than about 1000nm.    
     
     
         7 . A method according to  claim 6 , wherein said providing comprises adding to an aqueous medium a composition comprising cyclosporin dispersed in a combination of lower alkanol consisting of at least one of ethanol and propylene glycol and a polyoxyethylene surfactant.  
     
     
         8 . A method according to  claim 7 , wherein said polyoxyethylene surfactant is polysorbate  80 .  
     
     
         9 . A method according to  claim 7 , wherein said lower alkanol is present in from about 25 to 60 weight percent, said polyoxyalkylene surfactant is present in from about 20 to 50 weight percent, and said cyclosporin is present in from about 2.5 to 25 weight percent.  
     
     
         10 . A method according to  claim 7 , wherein said composition further comprises polyoxyethylene cosolvent of less than 2000 Daltons.  
     
     
         11 . A kit comprising cyclosporin, at least one of ethanol and propylene glycol, and polysorbate  80 .  
     
     
         12 . A kit according to  claim 11 , further comprising PEG 400 .  
     
     
         13 . A method for preparing a formulation according to  claim 1  comprising: 
 combining at least one of ethanol and propylene glycol with cyclosporin A to from a solution; and  
 combining said solution with a polyethyleneoxy surfactant to form a second solution, which upon dilution with water forms amorphous nanoparticles of said cyclosporin A.