Controlled release pharmaceutical compositions comprising a fumaric acid ester

Abstract

The present invention relates to controlled release pharmaceutical compositions comprising fumaric acid ester(s) as active substance(s). The compositions are suitable for use in the treatment of e.g. psoriasis or other hyperproliferative, inflammatory or autoimmune disorders and are designated to release the fumaric acid ester in a controlled manner so that local high concentrations of the active substance within the gastrointestinal tract upon oral administration can be avoided and, thereby, enabling a reduction in gastro-intestinal related side-effects.

1 .- 45 . (canceled) 
     
     
         46 . A controlled release pharmaceutical composition for oral use in the form of a capsule or a tablet comprising as an active substance one or more fumaric acid esters selected from di-(C 1 -C 5 )alkylesters of fumaric acid and mono-(C 1 -C 5 )alkylesters of fumaric acid, or a pharmaceutically acceptable salt thereof, wherein the release of the fumaric acid ester when subjected to an in vitro dissolution test employing 0.1 N hydrochloric acid as dissolution medium during the first 2 hours of the test and then 0.05 M phosphate buffer pH 6.5 as dissolution medium, wherein the dissolution profile is determined as described in the United States Pharmacopoeia at 37° C. and a rotation speed of 100 rpm using a rotating basket for a capsule and a paddle dissolution apparatus for a tablet is as follows: within the first 3 hours after start of the test at the most 70% w/w of the total amount of the fumaric acid ester contained in the composition is released. 
     
     
         47 . The controlled release pharmaceutical composition according to  claim 46 , wherein the release of the fumaric acid ester is as follows:
 within the first 4 hours after start of the test at the most 92% w/w of the total amount of the fumaric acid ester is released.   
     
     
         48 . The controlled release pharmaceutical composition according to  claim 46 , wherein the release of the fumaric acid ester is as follows:
 within the first 5 hours after start of the test at the most 94% w/w of the total amount of the fumaric acid ester is released.   
     
     
         49 . The controlled release pharmaceutical composition according to  claim 46 , wherein the release of the fumaric acid ester is as follows:
 within the first 6 hours after start of the test at the most 95% w/w of the total amount of the fumaric acid ester contained in the composition is released.   
     
     
         50 . The controlled release pharmaceutical composition according to  claim 46 , wherein the release of the fumaric acid ester is as follows:
 within the first 7 hours after start of the test at the most about 98% w/w of the total amount of the fumaric acid ester contained in the composition is released.   
     
     
         51 . The controlled release pharmaceutical composition according to  claim 46 , wherein the release of the fumaric acid ester is as follows:
 within the first 9 hours after start of the test at the most 99% w/w of the total amount of the fumaric acid ester contained in the composition is released.   
     
     
         52 . The controlled release pharmaceutical composition according to  claim 46 , wherein the release of the fumaric acid ester is as follows:
 within the first 12 hours after start of the test at the most 99% w/w of the total amount of the fumaric acid ester contained in the composition is released.   
     
     
         53 . The controlled release pharmaceutical composition according to  claim 46  comprising dimethylfumarate as the active substance.