Oral Dosage Forms of Methyl Hydrogen Fumarate and Prodrugs Thereof
AssigneeXenoPort, Inc.
InventorsSami Karaborni, Sarina Grace Harris Ma, Chen Mao, Ching Wah Chong, Peter Robert Prinz Freed, Mesut Ciper, Stefanie Krenzlin, David J. Wustrow, Peter A. Virsik
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Abstract
Improved oral dosage forms of methyl hydrogen fumarate and prodrugs thereof are disclosed. Methods of treating diseases such as multiple sclerosis and psoriasis using such dosage forms are also disclosed.
Claims49
An oral dosage form comprising:
- a core comprising a therapeutically effective amount of a compound selected from (i) methyl hydrogen fumarate (MHF), (ii) a prodrug of MHF, (iii) pharmaceutically acceptable salts of (i) or (ii), and (iv) combinations of any of the foregoing;
- a barrier layer surrounding said core, the barrier layer comprising a material that is (i) a weakly acidic (proton-donating) material having a pKa of greater than 8, (ii) a weakly basic (proton-accepting) material having a pKa of less than 2, (iii) a natural gum or polysaccharide derivative (iv) a neutral polymer salt, (v) a sugar, (vi) a lipid, or (vii) combinations of any of the foregoing;
- the barrier layer preventing direct contact between the core and an enteric coating;
- and
- the enteric coating surrounding said barrier layer and comprising an enteric polymer having carboxylic acid moieties, the enteric polymer (i) being soluble in aqueous solutions having a pH above 7.5, and (ii) starting to become soluble in an aqueous solution at a pH in the range of 4.5 to 7.5.
A method of making (N,N-Diethylcarbamoyl)methyl methyl (2E)but-2-ene-1,4-dioate-containing pharmaceutical pellets comprising:
- mixing the (N,N-Diethylcarbamoyl)methyl methyl (2E)but-2-ene-1,4-dioate in an aqueous medium;
- adding acetic acid to the aqueous medium;
- and
- maintaining the aqueous medium at a pH at or below 3.8.
A method of improving the yield of MHF-containing or MHF prodrug-containing pellets within a predetermined pellet size range during manufacture of said pellets, comprising:
- combining the MHF or the MHF prodrug with water, an extrusion aid, and a binder, to form a wet mixture;
- passing the mixture through a sieve, screen or die to form an extrudate;
- and spheronizing the extrudate to form pellets.
Dependencies are inferred from the claim text.