Controlled Release Dosage Form for Once Daily Administration of Dimethyl Fumarate

Abstract

A controlled release dosage form containing monomethyl fumarate, a compound that can be metabolized into monomethyl fumarate in vivo, or a pharmaceutically acceptable salt thereof or combinations thereof, wherein the monomethyl fumarate, a compound that can be metabolized into monomethyl fumarate in vivo, or a pharmaceutically acceptable salt thereof or combinations thereof is delivered to the subject. Also provided is a method of treating a disease or disorder (e.g., multiple sclerosis) by orally administering a controlled release dosage form containing monomethyl fumarate, a compound that can be metabolized into monomethyl fumarate in vivo, or a pharmaceutically acceptable salt thereof or combinations thereof, wherein the monomethyl fumarate, a compound that can be metabolized into monomethyl fumarate in vivo, or a pharmaceutically acceptable salt thereof or combinations thereof.

1 - 26 . (canceled) 
     
     
         27 . A mucoadhesive dosage form comprising an active pharmaceutical ingredient and one or more mucoadhesive polymers; wherein the active pharmaceutical ingredient is monomethyl fumarate, a compound that can be metabolized into monomethyl fumarate in vivo, a pharmaceutically acceptable salt thereof, or combinations thereof; and wherein the one or more mucoadhesive polymers comprises poly(vinyl pyrrolidone). 
     
     
         28 . The mucoadhesive dosage form of  claim 27 , wherein administration of said mucoadhesive dosage form to a subject provides one or more of the following pharmacokinetic parameters: (a) a mean plasma MMF AUC overall  ranging from about 4.81 h·mg/L to about 11.2 h·mg/L; (b) a mean plasma MMF AUC 0-12  ranging from about 2.4 h·mg/L to about 5.5 h·mg/L; and (c) a mean AUC 0-infinity  ranging from about 2.4 h·mg/L to about 5.6 h·mg/L. 
     
     
         29 . The mucoadhesive dosage form of  claim 27 , wherein upon administration of said mucoadhesive dosage form to a subject, the active pharmaceutical ingredient is retained in the small intestine of the subject for at least 3 hours. 
     
     
         30 . The mucoadhesive dosage form of  claim 29 , wherein the active pharmaceutical ingredient is retained in the small intestine of the subject for at least 5 hours. 
     
     
         31 . The mucoadhesive dosage form of  claim 29 , wherein the active pharmaceutical ingredient is retained in the small intestine of the subject for at least 6 hours. 
     
     
         32 . The mucoadhesive dosage form of  claim 29 , wherein the active pharmaceutical ingredient is retained in the small intestine of the subject for at least 7 hours. 
     
     
         33 . A controlled release dosage form comprising a matrix dosage form, said matrix dosage form comprising (a) an active pharmaceutical ingredient, (b) povidone, and (c) one or more pharmaceutically acceptable excipients; wherein the active pharmaceutical ingredient is monomethyl fumarate, a compound that can be metabolized into monomethyl fumarate in vivo, a pharmaceutically acceptable salt thereof, or combinations thereof. 
     
     
         34 . The controlled release dosage form of  claim 33 , wherein administration of said controlled release dosage form to a subject provides one or more of the following pharmacokinetic parameters: (a) a mean plasma MMF AUC overall  ranging from about 4.81 h·mg/L to about 11.2 h·mg/L; (b) a mean plasma MMF AUC 0-12  ranging from about 2.4 h·mg/L to about 5.5 h·mg/L; and (c) a mean AUC 0-infinity  ranging from about 2.4 h·mg/L to about 5.6 h·mg/L. 
     
     
         35 . The controlled release dosage form of  claim 33 , wherein upon administration of said controlled release dosage form to a subject, the active pharmaceutical ingredient is retained in the small intestine of the subject for at least 3 hours. 
     
     
         36 . The controlled release dosage form of  claim 35 , wherein the active pharmaceutical ingredient is retained in the small intestine of the subject for at least 5 hours. 
     
     
         37 . The controlled release dosage form of  claim 35 , wherein the active pharmaceutical ingredient is retained in the small intestine of the subject for at least 6 hours. 
     
     
         38 . The controlled release dosage form of  claim 35 , wherein the active pharmaceutical ingredient is retained in the small intestine of the subject for at least 7 hours. 
     
     
         39 . A method of treating multiple sclerosis in a subject in need thereof, comprising orally administering to the subject the controlled release dosage form of  claim 27 . 
     
     
         40 . A method of treating multiple sclerosis in a subject in need thereof, comprising orally administering to the subject the controlled release dosage form of  claim 33 .