# US 2018/0021286 A1 · Stabilized dialkyl fumarate compositions > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2018/0021286 A1 - Document ID: US20180021286A1 - Status: Published application - Kind: A1 - Application number: 15/548,017 - Filed: 2016-01-29 - Published: 2018-01-25 - Earliest claimed: 2015-02-02 - Assignees: Enspire Group LLC - Applicants: Enspire Group LLC - Inventors: Abdul Rashid; Zhang Julia Zhang; Minh Tran; Dahai Guo; Yi Zeng; Charchil Vejani; Hengsheng Adam Feng - Web page: https://patentgrep.com/patent/US20180021286A1 ## CPC - A61K 31/225: Polycarboxylic acids - A61K 9/10: Dispersions; Emulsions - A61K 9/4808: {characterised by the form of the capsule or the structure of the filling; Capsules containing small tablets; Capsules with outer layer for immediate drug release (capsules filled with granules or microparticles A61K9/16; filled with microcapsules or coated microparticles A61K9/50; with mixture of different granules, microcapsules, (coated) microparticles A61K9/5084)} - A61K 9/4858: {Organic compounds} - A61K 9/4866: {Organic macromolecular compounds} - A61K 9/4891: {Coated capsules; Multilayered drug free capsule shells (with drug coating for immediate release A61K9/4808; osmotic devices A61K9/0004)} - A61K 47/10: Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers - A61K 47/12: Carboxylic acids; Salts or anhydrides thereof - A61K 47/26: Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin - A61K 47/44: Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin (synthetic glycerides, e.g. medium-chain triglycerides, A61K47/14) - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) ## Abstract Stabilized liquid, suspension or gel compositions containing a dialkyl fumarate and comprising a vehicle which serves as a protective base, a pharmaceutically acceptable surfactant, and a pharmaceutically acceptable acidulant, and methods of preparing such compositions are disclosed. Capsules and other dosage forms containing the stabilized liquid, suspension or gel compositions are also disclosed. ## Claims ### Claim 1 A liquid, suspension or gel composition comprising: a) about 10-50% by weight of a dialkyl fumarate; bi) about 30-75% by weight of a vehicle comprising one or more compounds selected from the group consisting of pharmaceutically acceptable waxes, solid aliphatic alcohols, vegetable oils, hydrogenated vegetable oils, and mixtures of two or more thereof; or bii) about 30-85% by weight of a vehicle comprising one or more compounds selected from the group consisting of of poly(ethylene glycols); c) about 1-30% by weight of at least one pharmaceutically acceptable surfactant; and d) about 1-10% by weight of a pharmaceutically acceptable acidulant; based on the total weight of the composition. ### Claim 2 (depends on 1) The composition of claim 1 which has one or more of the following features: (a) said dialkyl fumarate and said vehicle are present in a ratio of about 2:15 to about 10:9 by weight; (b) said dialkyl fumarate and said surfactant are present in a ratio of about 2:3 to about 25:1 by weight; and (c) said dialkyl fumarate and said an acidulant are present in a ratio of about 1:1 to about 50:1 by weight. ### Claim at position 3 3-5. (canceled) ### Claim 6 (depends on 1) The composition of claim 1 where bii) comprises 30-75% by weight of PEG 400 and 0.2-10% by weight of PEG 1450. ### Claim 7 (canceled) ### Claim 8 (depends on 1) The composition claim 1, wherein dialkyl fumarate is the only active ingredient, and said dialkyl fumarate is dimethyl fumarate. ### Claim 9 (canceled) ### Claim 10 (depends on 1) The composition of claim 1, wherein said surfactant is selected from the group consisting of surfactants having an HLB of 4, or greater and mixtures of two or more thereof. ### Claim at position 9 11-14. (canceled) ### Claim 15 (depends on 1) The composition of claim 1, wherein the vehicle consists essentially of 45-60% by weight of sunflower oil, 0.5-5% by weight of bees wax, and 0.5-10% by weight of hydrogenated vegetable oil, based on the total weight of the composition. ### Claim 16 (depends on 1) The composition of claim 1, wherein the surfactant consists essentially of 1-15% by weight of polyoxyl-40 hydrogenated castor oil based on the total weight of the composition. ### Claim 17 (depends on 1) The composition of claim 1, wherein the acidulant consists essentially of 1-10% by weight of lactic acid based on the total weight of the composition. ### Claim 18 (depends on 1) A method of preparing a liquid, suspension or gel composition of claim 1, comprising: (a) heating the vehicle to a temperature of 65±5° C. with stirring for a first period of time to obtain a first mixture; (b) adding the surfactant into the first mixture with stirring at the same temperature to obtain a second mixture; (c) cooling the second mixture to ambient temperature to obtained a cooled second mixture; (d) adding the acidulant to the cooled second mixture with stirring at ambient temperature to obtain a third mixture; (e) adding dialkyl fumarate to the third mixture with stirring at the ambient temperature to obtain a fourth mixture; and (f) deaerating the fourth mixture, providing the composition. ### Claim 19 (depends on 1) A softgel capsule comprising a soft gelatin or soft non-gelatin shell, or a 2-piece hardshell capsule filled with the liquid, suspension or gel composition of claim 1. ### Claim at position 15 20-21. (canceled) ### Claim 22 (depends on 19) The capsule of claim 19, further comprising an enteric coating. ### Claim 23 (depends on 22) The capsule of claim 22, wherein said enteric coating comprises a controlled release polymer. ### Claim at position 18 24-29. (canceled) ### Claim 30 (depends on 31) The suspension composition of claim 31, wherein dimethyl fumarate is present in about 34.53%, lactic acid is present in about 4.32%, the vehicle is present in about 35.97%, polyoxyl-40 hydrogenated castor oil is present in about 10.07%; and sorbitan monooleate is present in about 15.11% by weight. ### Claim 31 A suspension composition comprising: a) about 10-50% by weight of dimethyl fumarate; b) about 30-85% of a pharmaceutically acceptable vehicle; ci) about 1-15% by weight of polyoxyl-40 hydrogenated castor oil; cii) about 1-20% by weight of sorbitan monooleate; and d) about 1-10% by weight of lactic acid; based on the total weight of the composition. ### Claim 32 (canceled) ### Claim 33 (depends on 31) A softgel capsule comprising a soft gelatin or soft non-gelatin shell, or a 2-piece hardshell capsule filled with the suspension composition of claim 31. ### Claim at position 23 34-35. (canceled) ### Claim 36 (depends on 33) The capsule of claim 33, further comprising an enteric coating. ### Claim 37 (depends on 36) The capsule of claim 36, wherein said enteric coating comprises a controlled release polymer. ### Claim 38 (canceled) ### Claim 39 A liquid, suspension or gel composition which releases dialkyl fumarate by a mechanism in which the formulation, upon interaction with an aqueous environment in vivo, forms an oil-in-water emulsion, releasing the dialkyl fumarate and making it bioavailable. ### Claim 40 (depends on 1) A unit dosage form suitable for oral administration to a patient, comprising the composition of claim 1, wherein said unit dosage form is a soft shell or hard shell capsule containing said composition and said capsule comprises a coating which does not release said composition until the pH of the surrounding medium is 3.5 or higher. ### Claim at position 29 41-43. (canceled) ### Claim 44 (depends on 40) The unit dosage form of claim 40, containing 240 mg or 480 mg of dimethyl fumarate. ### Claim 45 (canceled) ### Claim 46 (depends on 40) A method of treatment of multiple sclerosis, comprising administering to a patient in need thereof a treatment-effective dose of a dialkyl fumarate contained in the unit dosage form of claim 40. ### Claim 47 (canceled) ### Claim 48 (depends on 40) A method of treatment of patient having a condition characterized by at least one symptom chosen from neurodegeneration and neuroinflammation, comprising administering to a patient in need thereof a treatment-effective dose of a dialkyl fumarate contained in the unit dosage form of claim 40.