Pharmaceutical composition

Abstract

Pharmaceutical compositions comprising a cyclosporin in a novel galenic formulations for oral administration. The compositions typically comprise a cyclosporin, 1,2-propylene glycol, a mixed mono-, di- and tri-glyceride and a hydrophilic surfactant. Further a refined glycerol-transesterified corn oil is provided representing a mixed mono-, di- and tri-glyceride suitable for the novel formulation. Dosage forms include in particular oral dosage forms.

1 . A pharmaceutical composition comprising a cyclosporin as active ingredient in a carrier medium comprising: 
 1) 1,2-propylene glycol    2) a mixed mono-, di-, tri-glyceride, and    3) a surfactant.    
     
     
         2 . A composition according to    claim 1   , wherein component (2) comprises C 12 -C 20  fatty acid mono-, di- and tri-glycerides.  
     
     
         3 . A composition according to    claim 2   , wherein component (2) comprises linolenic, linoleic and oleic acids.  
     
     
         4 . A composition according to    claim 2   , wherein component (2) comprises a trans-esterification product of a vegetable oil.  
     
     
         5 . A composition according to    claim 4   , wherein the vegetable oil is corn oil.  
     
     
         6 . A composition according to    claim 4   , wherein the vegetable oil is transesterified with glycerol.  
     
     
         7 . A composition according to    claim 2   , wherein the free glycerol content is below 1%.  
     
     
         8 . A composition according to    claim 6   , wherein component (2) comprises Maisine.  
     
     
         9 . A composition according to    claim 6   , wherein component (2) comprises a “refined glycerol-transesterified corn oil”.  
     
     
         10 . A composition according to    claim 9    wherein component (2) comprises a composition which is a trans-esterification product of corn oil and glycerol comprising predominately of linoleic acid and oleic acid mono-, di- and tri-glycerides treated to enhance the unsaturated fatty acid component content of mono-, di- and tri-glycerides so that the linoleic acid and oleic acid mono-, di- and tri-glyceride content is in total 85% or more of the whole composition.  
     
     
         11 . A composition according to    claim 1   , wherein component (2) comprises from about 30% to about 40% monoglycerides, from about 45% to about 55% of di-glycerides and at least 5% of tri-glycerides by weight based on the total weight of component (2).  
     
     
         12 . A composition according to    claim 11    wherein component (2) comprises from about 32% to about 36% of monoglycerides, from about 45% to about 55% of di-glycerides, and from about 12% to about 20% of tri-glycerides by weight based on the total weight of component (2).  
     
     
         13 . A composition according to    claim 1   , wherein component (3) gas an HLB value of at least 10.  
     
     
         14 . A composition according to    claim 1   , wherein component (3) comprises a reaction product of a natural or hydrogenated castor oil and ethylene oxide.  
     
     
         15 . A composition according to    claim 1   , wherein (3) comprises Cremophor RH40.  
     
     
         16 . A composition according to    claim 1   ,wherein the carrier medium additionally comprises a hydrophilic phase co-component.  
     
     
         17 . A composition according to    claim 16   , wherein the hydrophilic phase co-component is ethanol.  
     
     
         18 . A composition according to    claim 1   , which is a micro-emulsion preconcentrate.  
     
     
         19 . A composition according to    claim 1    in unit dosage form.  
     
     
         20 . A composition according to    claim 19   , comprising a gelatine encapsulated form.  
     
     
         21 . A composition according to    claim 1    additionally comprising water or an aqueous phase and which is a microemulsion.  
     
     
         22 . A composition according to    claim 1   , wherein component (1) plus any hydrophilic phase co-component present comprises from 10 to 35% by weight of the hydrophilic phase component (1) plus components (2) an (3).  
     
     
         23 . A composition according to    claim 22   , wherein the hydrophilic phase co-component is present in an amount of from about 25 to 75% of the total weight of component (3) and the hydrophilic phase co-component.  
     
     
         24 . A composition according to    claim 1   , wherein the component (2) is present in an amount of from 20 to 40% based on the total weight of hydrophilic phase component(s) plus component (2) and (3).  
     
     
         25 . A composition according to    claim 1   , wherein the component (3) is present in an amount of from 30 to 60% based on the total weight of hydrophilic phase component(s) plus component (2) and (3).  
     
     
         26 . A composition according to    claim 1    containing from 7.5 to 15% of cyclosporin.  
     
     
         27 . A composition according to    claim 1    containing Ciclosporin as the cyclosporin.  
     
     
         28 . A composition according to    claim 1    containing [0-(2-hydroxyethyl)-(D)Ser] 8 -Ciclosporin as the cyclosporin.  
     
     
         29 . A composition according to    claim 1    containing [3′-deshydroxy-3′-keto-MeBmt] 1 -[Val] 2 -Ciclosporin as the cyclosporin.  
     
     
         30 . A composition according to    claim 1    containing Cyclosporin G as the cyclosporin.