Fumarate ester dosage forms
View Patent ↗Described herein are pharmaceutical compositions comprising fumarate esters, methods for making the same, and methods for treating subjects in need thereof. In particular, oral controlled release pharmaceutical compositions comprising fumarate esters suspended in liquid matrices are described. One embodiment described herein is a pharmaceutical composition comprising fumarate esters suspended in a lipid or lipophilic liquid with enhanced bioavailability.
1. A pharmaceutical composition comprising about 80 mg to about 110 mg of dimethyl fumarate or monomethyl fumarate in an immediate releasing single-phase non-aqueous liquid vehicle.
2. The composition of claim 1 , wherein the liquid comprises mono- and di-glycerides, polyvinylpyrrolidone, polyoxyl 40 hydrogenated castor oil, and lactic acid.
3. The composition of claim 1 , wherein the weight ratio of the fumarate ester to non-aqueous liquid is about 1:2.
4. The composition of claim 1 , wherein the fumarate ester is dimethyl fumarate.
5. The composition of claim 1 , wherein the fumarate ester is monomethyl fumarate.
6. The composition of claim 1 , wherein the composition is encapsulated in a soft capsule.
7. The composition of claim 1 , wherein the composition is encapsulated in an enterically coated soft capsule.
8. The composition of claim 1 , where upon administration to a subject, the fumarate ester activates a nuclear factor erythroid-derived 2-like (Nrf2) dependent pathway in the subject.
9. The composition of claim 1 , wherein two more doses of the composition are bioequivalent to 240 mg dimethyl fumarate provided as enterically coated minitablets.
10. A method of treating multiple sclerosis comprising administering to a subject one or more dosage forms that provide about 80 mg to about 110 mg or about 180 mg to about 220 mg of fumarate ester comprising dimethyl fumarate or monomethyl fumarate in an immediate releasing single-phase non-aqueous liquid vehicle.
11. The method of claim 10 , wherein the liquid comprises mono- and di-glycerides, polyvinylpyrrolidone, polyoxyl 40 hydrogenated castor oil, and lactic acid.
12. The method of claim 10 , wherein the fumarate ester is dimethyl fumarate.
13. The method of claim 10 , wherein the fumarate ester is monomethyl fumarate.
14. The method of claim 10 , wherein the composition is encapsulated in a soft capsule.
15. The method of claim 10 , wherein the composition is encapsulated in an enterically coated soft capsule.
16. The method of claim 10 , where upon administration, the fumarate ester activates a nuclear factor erythroid-derived 2-like (Nrf2) dependent pathway in the subject.
17. The method of claim 10 , wherein the administration comprises:
(a) administering two dosage forms simultaneously comprising about 80 mg to about 110 mg of fumarate ester twice per day (BID);
(b) administering one dosage from comprising about 160 to about 220 mg of fumarate ester twice per day (BID); or
(c) administering one dosage from comprising about 80 mg to about 110 mg of fumarate ester four times per day.
18. The method of claim 10 , wherein the administration comprises a daily dosage of about 160 mg, about 170 mg, about 180 mg, about 190 mg, about 200 mg, about 210 mg, or about 220 mg of the fumarate ester.
19. The method of claim 10 , wherein the 180 mg to about 220 mg of fumarate ester are bioequivalent to 240 mg dimethyl fumarate provided as enterically coated minitablets.
20. The method of claim 10 , wherein the subject achieves a reduction of annualized relapse rate relative to baseline experiencing one or more of flushing, abdominal pain, diarrhea, or nausea at a rate of less than about 20%.