Oral dosage forms having a high loading of a methyl hydrogen fumarate prodrug

Abstract

Oral dosage forms and granulations with a high loading of a methyl hydrogen fumarate prodrug are disclosed.

1 . A solid pharmaceutical granulation comprising at least about 95 wt % (N,N-Diethylcarbamoyl)methyl methyl (2E)but-2-ene-1,4-dioate and one or more pharmaceutically acceptable excipients. 
     
     
         2 . The granulation of  claim 1 , comprising at least about 97 wt % (N,N-Diethylcarbamoyl)methyl methyl (2E)but-2-ene-1,4-dioate. 
     
     
         3 . The granulation of  claim 1 , wherein the pharmaceutically acceptable excipient comprises a binder. 
     
     
         4 . The granulation of  claim 3 , wherein the binder comprises a polymer selected from hydroxypropyl cellulose, hydroxypropylmethyl cellulose, polyvinyl pyrrolidone and combinations thereof. 
     
     
         5 . A mixture comprising the solid granulation of  claim 1 , and at least one additional pharmaceutically acceptable excipient. 
     
     
         6 . The mixture of  claim 5 , wherein the at least one additional excipient is selected from fillers, diluents, binders, lubricants, disintegrants, glidants, sustained release agents and combinations thereof. 
     
     
         7 . The mixture of  claim 5 , comprising a glidant, so as to improve flowability of said mixture. 
     
     
         8 . The mixture of  claim 7 , comprising up to about 3 wt % silicon dioxide glidant. 
     
     
         9 . The mixture of  claim 7 , comprising up to about 1 wt % silicon dioxide glidant. 
     
     
         10 . The mixture of  claim 7 , comprising about 0.1 to about 0.5 wt % silicon dioxide glidant. 
     
     
         11 .- 18 . (canceled) 
     
     
         19 . A pharmaceutical tablet dosage form, the tablet having a core and one or more coatings surrounding the core, the core comprising from about 70 wt % to about 98 wt % (N,N-Diethylcarbamoyl)methyl methyl (2E)but-2-ene-1,4-dioate. 
     
     
         20 . The pharmaceutical tablet dosage form of  claim 19 , wherein the core comprises from about 80 wt % to about 97 wt % (N,N-Diethylcarbamoyl)methyl methyl (2E)but-2-ene-1,4-dioate. 
     
     
         21 . The pharmaceutical tablet dosage form of  claim 19 , including at least one pharmaceutically acceptable excipient. 
     
     
         22 . The pharmaceutical tablet dosage form of  claim 21 , wherein the excipient is selected from fillers, diluents, binders, lubricants, disintegrants, glidants, sustained release agents and combinations thereof. 
     
     
         23 . The pharmaceutical tablet dosage form of  claim 19 , comprising about 5 wt % to about 15 wt % of hydroxypropylmethyl cellulose. 
     
     
         24 . The pharmaceutical tablet dosage form of  claim 23 , wherein the dosage form is a sustained release dosage formulation. 
     
     
         25 . (canceled) 
     
     
         26 . The pharmaceutical tablet dosage form of  claim 19 , wherein in a sodium phosphate dissolution medium buffered to pH 6.8, maintained at 37° C. and stirred at 100 rpm, the dosage form releases 90 wt % of the (N,N-Diethylcarbamoyl)methyl methyl (2E)but-2-ene-1,4-dioate within 0.5 to 24 hours. 
     
     
         27 . A method of treating a disease in a subject comprising orally administering a pharmaceutical composition to a subject in need of such treatment, wherein the pharmaceutical composition comprises a solid pharmaceutical granulation comprising at least about 95 wt % (N,N-Diethylcarbamoyl)methyl methyl (2E)but-2-ene-1,4-dioate and one or more pharmaceutically acceptable excipients. 
     
     
         28 . The method of  claim 27 , wherein the disease is multiple sclerosis or psoriasis. 
     
     
         29 . (canceled) 
     
     
         30 . The method of  claim 27 , wherein the disease is selected from Parkinson's disease, amyotrophic lateral sclerosis (ALS), Huntington's disease, Alzheimer's disease, lupus, Crohn's disease, psoriatic arthritis and ankylosing spondylitis.