Ophthalmic compositions comprising ciclosporin

Abstract

The present invention relates to compositions in the form of a clear solution comprising ciclosporin with low residual water content and 1-perfluorobutyl-pentane. The compositions may be used for topical administration to the eye.

1 . A composition in the form of a clear solution comprising ciclosporin dissolved in 1-perfluorobutyl-pentane, wherein the composition is essentially free of a co-solvent, and wherein the composition has a residual water content of less than about 0.03 mg/mL. 
     
     
         2 . The composition according to  claim 1 , wherein the concentration of ciclosporin at 15-25° C. is from about 0.5 to 4.8 mg/mL. 
     
     
         3 . The composition according to any preceding claim, wherein the co-solvent is ethanol. 
     
     
         4 . The composition according to any preceding claim, wherein the solution is thermodynamically stable at 15-25° C. 
     
     
         5 . A composition according to any of the preceding claims for use as a medicine. 
     
     
         6 . The composition for use according to  claim 5 , wherein the composition for use in the treatment of keratoconjunctivitis sicca or a symptom thereof; or for use in the treatment of meibomian gland dysfunction or a symptom thereof. 
     
     
         7 . A composition obtainable by dissolving ciclosporin with a water content of less than about 1.0 wt %, based on the total weight of the ciclosporin, in 1-perfluorobutyl-pentane. 
     
     
         8 . The composition according to  claim 7 , wherein the ciclosporin is dissolved in the absence of a co-solvent. 
     
     
         9 . The composition according to  claim 7  or  8 , wherein the concentration of ciclosporin dissolved in the composition at 15-25° C. is greater than about 2.6 mg/mL. 
     
     
         10 . A method for the preparation of a composition in the form of a clear solution comprising ciclosporin dissolved in 1-perfluorobutyl-pentane, and wherein the composition is essentially free of a co-solvent, the method comprising the steps of a) providing ciclosporin with a water content of less than about 1.0 wt % based on the total weight of the ciclosporin, and b) dissolving said ciclosporin in 1-perfluorobutyl-pentane. 
     
     
         11 . The method according to  claim 10 , wherein step a) of providing ciclosporin with a water content of less than about 1.0 wt % based on the total weight of ciclosporin, comprises a step of drying ciclosporin with a water content of about 1.6 wt %, or greater than about 1.6 wt % based on the total weight of the ciclosporin. 
     
     
         12 . The method according to  claim 10  or  11 , wherein step a) comprises drying ciclosporin under vacuum, optionally in the presence of a water-desiccant or drying agent. 
     
     
         13 . A pharmaceutical kit, comprising:
 (i.) a composition as defined in any of the  claim 1 - 4  or  7 - 9 ;   (ii.) a container adapted for holding the composition, wherein the container has a dispensing means adapted for topical administration of the composition to the eye or ophthalmic tissue;   (iii.) optionally, a water-desiccant; and   (iv.) optionally, instructions for use of the kit in the treatment of kerato-conjunctivitis sicca or a symptom thereof, or for use of the kit in the treatment of meibomian gland dysfunction or a symptom thereof.