Novel cyclosporin galenic forms

Abstract

Pharmaceutical compositions comprising a cyclosporin as active ingredient, a fatty acid triglyceride, a glycerol fatty acid partial ester or propylene glycol or sorbitol complete or partial ester, preferably, and a tenside having an HLB of at least 10.

1 . A pharmaceutical composition comprising: 
 a) a cyclosporin as active ingredient in a carrier medium comprising    b) a fatty acid triglyceride and    c) a glycerol fatty acid partial ester or propylene glycol or sorbitol complete or partial ester.    
     
     
         2 . A pharmaceutical composition comprising 
 a) a cyclosporin as active ingredient in a carrier medium comprising    b+c) a transesterification product of a vegetable oil with glycerol, propylene glycol or sorbitol.    
     
     
         3 . A composition according to  claim 2  comprising 
 b+c) a transesterification product of a natural vegetable oil and glycerol or sorbitol.  
 
     
     
         4 . A composition according to  claim 3  for oral administration.  
     
     
         5 . A composition according to  claim 3 , wherein (a) is selected from the group consisting of Ciclosporin, (Dihydro-MeBmt) 1 -(Val) 2 -Ciclosporin and (Nva) 2 -Ciclosporin.  
     
     
         6 . A composition according to  claim 3 , wherein (b+c) is a corn oil, almond oil, ground-nut oil, olive oil or palm oil trans-esterification product.  
     
     
         7 . A composition according to  claim 6 , wherein (b+c) is a corn oil trans-esterification product.  
     
     
         8 . A composition according to  claim 3 , wherein (b+c) is a trans-esterification product of a vegetable oil and glycerol.  
     
     
         9 . A composition according to  claim 3 , wherein (b+c) is a trans-esterification product of a vegetable oil and sorbitol.  
     
     
         10 . A composition according to  claim 3 , wherein the amount of free glycerol plus any other free mono- or poly-ol present in (b+c) is less than 10%, preferably less than 5%, by weight.  
     
     
         11 . A composition according to  claim 3 , wherein the amount of mono-glyceride present in (b+c) is ca. 25-50%, preferably 30-45% by weight.  
     
     
         12 . A composition according to  claim 8 , wherein the amount of free glycerol present in (b+c) is less than 10%, preferably less than 5%, more preferably ca. 4% by weight.  
     
     
         13 . A composition according to  claim 8 , wherein the amount of mono-glyceride present in (b+c) is 35-50% by weight, preferably 40-45% by weight.  
     
     
         14 . A composition according to  claim 8 , wherein the amount of di-glyceride present in (b+c) is less than 40% and the amount of tri-glyceride present is less than 10% by weight.  
     
     
         15 . A composition according to  claim 9 , wherein the amount of free glycerol plus free sorbitol present in (b+c) is less than 5%, preferably ca. 1-2% by weight.  
     
     
         16 . A composition according to  claim 9 , wherein the amount of mono-glyceride present in (b+c) is 30 to 40% by weight, preferably ca. 35% by weight.  
     
     
         17 . A composition according to  claim 12 , wherein (b+c) is a corn-oil trans-esterification product.  
     
     
         18 . A composition according to  claim 3  additionally comprising: 
 d) a pharmaceutically acceptable solvent or diluent miscible with (b+c) and reducing, or capable of reducing, the viscosity of (b+c).  
 
     
     
         19 . A composition according to  claim 18 , wherein (d) comprises a trans-esterification product of a natural vegetable oil triglyceride and a polyalkylene poly-ol.  
     
     
         20 . A composition according to  claim 18 , wherein (d) comprises ethanol.  
     
     
         21 . A composition according to  claim 15 , wherein (d) comprises an esterification product of caprylic acid and caproic acid with glycerol.  
     
     
         22 . A composition according to  claim 3  additionally comprising: 
 e) a pharmaceutically acceptable emulsifying agent.  
 
     
     
         23 . A composition according to  claim 22 , wherein (d) comprises a reaction product of a natural or hydrogenated castor oil and ethylene oxide.  
     
     
         24 . A composition according to  claim 3  in admixture with a pharmaceutically acceptable base material, the admixture being formed as, or capable of being formed into, a solid unit dosage.  
     
     
         25 . A composition according to  claim 24  wherein the pharmaceutically acceptable base material comprises a natural fat, in particular a natural vegetable fat such as cacao fat or cacao butter.  
     
     
         26 . A composition according to  claim 24  wherein the pharmaceutically acceptable base material comprises a chocolate base, for example couverture chocolate.  
     
     
         27 . A composition according to  claim 1  comprising: 
 a) a cyclosporin as active ingredient in a carrier medium comprising  
 b) a fatty acid triglyceride  
 c) a glycerol fatty acid partial ester or propylene glycol or sorbitol complete or partial ester, and  
 e′) a tenside having an HLB of at least 10.  
 
     
     
         28 . Composition according to  claim 27  wherein components (b) and (c) consist or consist essentially of the individual components of a trans-esterification product of a vegetable oil with glycerol, said composition: 
 i) being free or substantially free of ethanol; or  
 ii) comprising Ciclosporin or [Nva] 2 -Ciclosporin as component a); or  
 iii) comprising components (a) and (e′) in a ratio of 1: at least 1 p.p.w.  
 
     
     
         29 . Composition according to  claim 27 , wherein (a) is present in an amount of from about 2 to about 20% by weight based on the total weight of components (a) to (c) and (e′) inclusive.  
     
     
         30 . Composition according to  claim 27  wherein (d) comprises the reaction product of a natural or hydrogenated castor oil and ethylene oxide, a polyoxyethylene-sorbitan-fatty acid ester, a polyoxyethylene fatty acid ester, a polyoxyethylene-polyoxypropylene co-polymer or block co-polymer, dioctylsuccinate, di-[2-ethylhexyl]-succinate, a phospholipid, a propylene glycol mono- or di-fatty acid ester or sodium lauryl sulfate.  
     
     
         31 . Composition according to  claim 27  wherein (a) and (e′) are present in a ratio of about 1:1 to 25 p.p.w. [(a):(e)].  
     
     
         32 . Composition according to  claim 27  comprising a component (a) and a component (e′) as defined in  claim 27  and [(b)+(c)] a transesterification product of a vegetable oil and glycerol, propylene glycol or sorbitol.  
     
     
         33 . Composition according to  claim 32  wherein (b) and (c) consist or consist essentially of the individual components (b) and (c) of a component [(b)+(c)] as defined in  claim 32 .  
     
     
         34 . Composition according to  claim 33  wherein (a) and [(b)+(c)] are present in a ratio of about 1:0.75 to 35 p.p.w. [(a):[(b)+(c)]].  
     
     
         35 . Composition according to  claim 27  comprising at least one ingredient which consists or consists essentially of a component or components (b) as defined in  claim 27  or of a component or components (c) as defined in  claim 27 .  
     
     
         36 . Composition according to  claim 27  wherein (c) comprises a glycerol fatty acid partial ester or acetylated derivative thereof.  
     
     
         37 . Composition according to  claim 27  wherein (b) and (c) are present in a ratio of about 1:0.02 to 3.0 p.p.w. [(b):(c)].