Pharmaceutical formulation comprising one or more fumaric acid esters in an erosion matrix

Abstract

A pharmaceutical formulation comprising an erosion matrix comprising one or more fumaric acid esters as well as one or more rate-controlling agents, wherein erosion of said erosion matrix permits controlled release of said fumaric acid ester(s).

1 .- 46 . (canceled) 
     
     
         47 . A method of treating psoriasis, psoriatic arthritis, neurodermatitis, inflammatory bowel disease, Crohn's disease, and ulcerative colitis, polyarthritis, multiple sclerosis, juvenile-onset diabetes mellitus, Hashimoto's thyroiditis, Grave's disease, systemic lupus erythematosus, Sjogren's syndrome, Pernicious anemia, Chronic active (lupoid) hepatitis, Rheumatoid arthritis, lupus nephritis, myasthenia gravis, uveitis, refractory uveitis, vernal conjunctivitis, pemphigus vulgaris, scleroderma, optic neuritis, radicular pain, pain associated with radiculopathy, neuropathic pain, sciatica/sciatic pain, organ transplantation rejection, sarcoidosis, necrobiosis lipoidica or granuloma annulare, which method comprises administering orally to a patient in need thereof an effective dosage of a pharmaceutical formulation in the form of an erosion matrix tablet comprising:
 a) a tablet core comprising
 i) 10% to 80% by weight of 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, as an active substance, and 
 ii) 1% to 50% by weight of one or more rate-controlling agents; and 
   b) an enteric coating, wherein said enteric coating is applied at a level of 1.5% to 3.5% by weight of the tablet core;   wherein erosion of said erosion matrix permits controlled or sustained release of said active substance.   
     
     
         48 . The method according to  claim 47 , which is a method for treating psoriasis. 
     
     
         49 . The method according to  claim 47 , which is a method for treating psoriatic arthritis. 
     
     
         50 . The method according to  claim 47 , which is a method for treating multiple sclerosis. 
     
     
         51 . The method according to  claim 47 , which is a method for treating rheumatoid arthritis. 
     
     
         52 . The method according to  claim 47 , wherein the tablet core comprises:
 i) 30% to 60% by weight of the one or more fumaric acid esters, and   ii) 3% to 40% by weight of the one or more rate-controlling agents.   
     
     
         53 . The method according to  claim 47 , wherein the erosion matrix is a monolithic erosion matrix. 
     
     
         54 . The method according to  claim 47 , wherein the rate-controlling agent is a water-soluble polymer. 
     
     
         55 . The method according to  claim 54 , wherein the water-soluble polymer is selected from the group consisting of hydroxypropyl methyl cellulose, hydroxypropyl cellulose, methyl cellulose, and carboxymethyl cellulose. 
     
     
         56 . The method according to  claim 55 , wherein the water-soluble polymer is hydroxypropyl cellulose. 
     
     
         57 . The method according to  claim 47 , wherein the tablet core further comprises a binder. 
     
     
         58 . The method according to  claim 57 , wherein the tablet core comprises:
 i) 40% to 60% by weight of one or more fumaric acid esters selected from the group consisting of di-(C 1 -C 5 )alkylesters of fumaric acid and mono-(C 1 -C 5 )alkylesters of fumaric acid, and a pharmaceutically acceptable salt thereof, as an active substance,   ii) 4% to 6% by weight of a rate-controlling agent, and   iii) 35% to 55% by weight of a binder.   
     
     
         59 . The method according to  claim 47 , wherein the fumaric acid ester is selected from the group consisting of dimethylfumarate, diethylfumarate, dipropylfumarate, dibutylfumarate, dipentylfumarate, methyl-ethylfumarate, methyl-propylfumarate, methyl-butylfumarate, methyl-pentylfumarate, monomethylfumarate, monoethylfumarate, monopropylfumarate, monobutylfumarate, and monopentylfumarate, or a pharmaceutically acceptable salt thereof. 
     
     
         60 . The method according to  claim 59 , wherein the tablet core comprises a pharmaceutically acceptable salt of a mono-(C 1 -C 5 )alkylester of fumaric acid as the active substance. 
     
     
         61 . The method according to  claim 47 , wherein the tablet core comprises dimethylfumarate as the active substance. 
     
     
         62 . The method according to  claim 47 , wherein the tablet core comprises monomethylfumarate or a pharmaceutically acceptable salt thereof as the active substance. 
     
     
         63 . The method according to  claim 58 , wherein the tablet core comprises:
 i) 40% to 55% by weight of dimethyl fumarate,   ii) 4% to 6% by weight of hydroxypropyl cellulose, and   iii) 35% to 55% by weight of lactose.   
     
     
         64 . The method according to  claim 47 , wherein the erosion matrix does not contain a water-insoluble polymer.