Fumarate ester pharmaceutical compositions

Inventors

Dyakonov, Tatyana • Agnihotri, Sunil • Fatmi, Aqeel A.

Assignees

Banner Life Sciences LLC

Abstract

Described herein are pharmaceutical compositions comprising fumarate esters, methods for making the same, and methods for treating subjects in need thereof. In particular, oral pharmaceutical compositions comprising fumarate esters are described.

Core Innovation

The disclosure relates to oral controlled or delayed release pharmaceutical compositions comprising fumarate esters, including dimethyl fumarate and monomethyl fumarate. The compositions use a single phase non-aqueous liquid vehicle comprising a suspension of fumarate esters or salts, with R1 and R2 independently representing hydrogen or methyl, and a lipid or lipophilic matrix containing solid fumarate ester particles in defined particle size distribution ranges.

The compositions include neutralizing and anti-hydrolysis agents, including organic acids such as lactic acid, in combination with matrix excipients including mono- and di-glycerides, polyvinylpyrrolidone, polyoxyl 40 hydrogenated castor oil, and polysorbate 80. Solid milled or micronized fumarate ester particles are used, and capsule shell components employ film-forming and enteric acid-insoluble polymers such as gelatin and methacrylate copolymers with specified plasticizers or solvents.

Enteric capsule shells are described as resistant at pH about 1.2 for at least about 2 hours and beginning to dissolve near pH about 6.8, enabling delayed release. Manufacturing is described using rotary die encapsulation after casting capsule shell films to form enteric soft capsules, and dissolution and stability data are provided to show retained enteric integrity in gastric conditions and controlled fumarate ester release when intestinal pH is reached.

Claims Coverage

The independent claim identified covers an oral immediate release pharmaceutical composition with a single-phase non-aqueous liquid vehicle containing a suspension of fumarate esters or salts, where R1 and R2 are hydrogen or methyl. The refinements include additional excipient constraints, substituent selection, encapsulation for delayed release, enteric soft capsule configurations, fumarate ester particle handling, and a stability requirement.

Overall, the claim set focuses on an oral fumarate-ester formulation in a single phase non-aqueous liquid vehicle with specified R1/R2 definitions, refined by excipient and content constraints including lactic acid and specific lipid or lipophilic components, optional capsule encapsulation and enteric soft capsule delayed release, and an explicit stability requirement at 25°C for at least 1 year.

Stated Advantages

Documented Applications