Fumarate ester pharmaceutical compositions
Inventors
Dyakonov, Tatyana • Agnihotri, Sunil • Fatmi, Aqeel A.
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-10105337-B2
Publication Date
2018-10-23
Expiration Date
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 invention relates to an oral immediate release pharmaceutical composition containing one or more fumarate esters or salts thereof, carried in a single phase non-aqueous vehicle. The fumarate esters are defined by a formula in which R1 and R2 independently represent hydrogen or linear, branched, or cyclic saturated or unsaturated C1-20 alkyl radicals, optionally substituted with halogen, hydroxy, C1-4 alkoxy, nitro, or cyano, and the composition comprises about 60 mg to about 200 mg of the one or more fumarate esters or salts.
The disclosure further provides controlled design of the oral presentation, including enteric soft capsule formats, in which enteric acid-insoluble polymers are used to reduce gastric release. It describes using capsule shell and vehicle/matrix compositions together with neutralizing agents so that release is tailored toward immediate, controlled, delayed, or extended release behavior.
A key aspect of the formulation design is reduction of side effects associated with fumarate ester delivery, including gastrointestinal side effects. The invention also addresses fumarate ester sublimation during manufacturing and storage by using formulation approaches that mitigate sublimation, and stability is reported under conditions including ICH-type storage, with chemical assay and degradation products used to support stability over time.
Claims Coverage
The explicitly provided claim content identifies one independent claim and several dependent refinements. The coverage centers on an oral immediate release pharmaceutical composition with a single phase non-aqueous vehicle and a defined fumarate ester formula, with additional features directed to enteric soft capsule format, delayed release, milled or micronized particle form, and constrained formulation components.
Single-phase non-aqueous fumarate-ester vehicle for oral immediate release
An oral immediate release pharmaceutical composition comprising a single phase non-aqueous vehicle comprising about 60 mg to about 200 mg of one or more fumarate esters or salts thereof.
Defined fumarate ester R1/R2 substituent formula
The fumarate ester or salt is having a formula in which R1 and R2 independently represent hydrogen or a linear, branched, or cyclic saturated or unsaturated C1-20 alkyl radical, optionally substituted with halogen, hydroxy, C1-4 alkoxy, nitro, or cyano.
Enteric soft capsule presentation
The composition is encapsulated in an enteric soft capsule.
Delayed release provided by enteric soft capsule
An enteric soft capsule provides delayed release of the fumarate ester.
Milled or micronized fumarate ester particles
The fumarate ester is provided as milled or micronized particles.
Constrained component proportions within the formulation
The composition specifies about 25% to about 50% fumarate esters or salts, about 40% to about 54% mono- and di-glycerides, about 1% to about 10% polyvinylpyrrolidone, about 2% to about 10% polyoxyl 40 hydrogenated castor oil, and about 5% lactic acid.
The claim coverage focuses on an oral immediate release fumarate-ester composition in a single phase non-aqueous vehicle defined by an R1/R2 substituent formula. The dependent claim content further narrows embodiments to enteric soft capsule formats with delayed release, milled or micronized fumarate ester particles, and specified formulation component ranges.
Stated Advantages
Prevents gastric release and reduces GI side effects.
Reduces fumarate ester sublimation during manufacturing and storage.
Enables tailored release kinetics including immediate, controlled, delayed, and extended release behavior.
Provides stable pharmaceutical performance under storage conditions, supported by chemical assay and degradation products.
Documented Applications
Therapeutic use for multiple sclerosis.
Therapeutic use for psoriasis.
Therapeutic use for other autoimmune/neurodegenerative disorders (not further enumerated in the provided partial content).
Interested in licensing this patent?