RU2021120840A - COMPOSITIONS BASED ON BRANAPLAM FOR ORAL USE - Google Patents

Claims (39)

1. Pharmaceutical composition containing A) a compound of formula (I),

(I) or a pharmaceutically acceptable salt thereof, and B) a pharmaceutically acceptable cyclodextrin or a combination of pharmaceutically acceptable cyclodextrins. 2. The pharmaceutical composition according to claim 1, wherein the compound of formula (I) is in the form of its hydrochloride salt. 3. Pharmaceutical composition according to claim 1 or 2, wherein the cyclodextrin is beta-cyclodextrin, e.g. selected from the group consisting of 2-hydroxypropyl-beta-cyclodextrin, beta-cyclodextrin sulfobutyl ether, beta-cyclodextrin, methyl-beta-cyclodextrin , hydroxyethyl-beta-cyclodextrin, ethyl-beta-cyclodextrin, butyl-beta-cyclodextrin, succinyl-(2-hydroxypropyl)-beta-cyclodextrin, heptakis(2,3,6-tri-O-methyl)-beta-cyclodextrin, heptakis(2,3,6-tri-O-benzoyl)-beta-cyclodextrin, beta-cyclodextrinphosphate sodium salt, beta-cyclodextrin sulfate sodium salt, triacetyl-beta-cyclodextrin, heptakis(6-O-sulfo)-beta-heptanasodium salt cyclodextrin, carboxymethyl-beta-cyclodextrin sodium salt, beta-cyclodextrin sulfobutyl ether sodium salt and 6-O-p-toluenesulfonyl-beta-cyclodextrin. 4. A pharmaceutical composition according to any one of the preceding claims, wherein the composition is a liquid composition. 5. Pharmaceutical composition according to any one of the preceding claims, wherein the cyclodextrin (B) is 2-hydroxypropyl-beta-cyclodextrin. 6. Pharmaceutical composition according to any one of paragraphs. 1-4, wherein the cyclodextrin (B) is beta-cyclodextrin sulfobutyl ether. 7. A pharmaceutical composition according to any one of the preceding claims, wherein the concentration of a compound of formula I, or any pharmaceutically acceptable salt thereof, is in the range of from about 1 mg/mL to about 30 mg/mL, for example, in the range from about 3 mg/mL to about 10 mg/ml. 8. A pharmaceutical composition according to any one of the preceding claims, wherein the cyclodextrin is present at a concentration that is in the range of 2 percent to 25 percent (w/v). 9. A pharmaceutical composition according to any one of the preceding claims, wherein the pH of the composition is in the range of 3.5 to 9, e.g., about 4. 10. A pharmaceutical composition according to any one of the preceding paragraphs, wherein said composition contains: A) a compound of formula I or a pharmaceutically acceptable salt thereof at a concentration of 1 mg/ml to 30 mg/ml, B) 2-hydroxypropyl-beta-cyclodextrin at a concentration that is in the range from 2 percent to 25 percent (w/v), for example, in the range from 10 percent to 20 percent (w/v). and where the pH of the composition is approximately 4.0. 11. A pharmaceutical composition according to any one of the preceding claims, wherein the composition further comprises at least one taste masking agent, for example sucralose. 12. A pharmaceutical composition according to any one of the preceding claims, wherein the composition further comprises at least one flavoring agent, for example vanilla. 13. A pharmaceutical composition according to any one of the preceding paragraphs, wherein said composition contains: a) the hydrochloride salt of the compound of formula (I) at a concentration of 3.5 mg/ml, b) 2-hydroxypropyl-beta-cyclodextrin at a concentration of 17.5 percent (w/v), c) sucralose at a concentration of 0.05 percent (w/v), d) vanilla at a concentration of 0.1 percent (w/v), e) water, and wherein the pH of the composition is about 4.0 or greater. 14. Pharmaceutical composition according to any one of paragraphs. 1-12, where said composition contains: a) a compound of formula I or a pharmaceutically acceptable salt thereof [for example the hydrochloride salt of a compound of formula (I)] at a concentration of 1 mg/ml to 30 mg/ml, for example 3.5 mg/ml, b) a pharmaceutically acceptable cyclodextrin (for example, 2-hydroxypropyl-beta-cyclodextrin) at a concentration of 10.0 percent (w/v), c) at least one taste masking agent, for example sucralose, at a concentration of 0.05% to 0.5% (w/v), for example 0.05% (w/v), d) optionally at least one flavor, eg vanilla, at a concentration of 0.05% to 0.2% (w/v), eg 0.1% (w/v). e) water, and wherein the pH of the composition is about 4.0 or greater (eg, about 4 to about 7). 15. A pharmaceutical composition according to any one of the preceding claims, wherein the composition is substantially free of preservatives. 16. Pharmaceutical composition according to any one of the preceding paragraphs for use as a drug, for example, a drug to be administered orally. 17. A pharmaceutical composition according to any of the preceding claims for use in the treatment or prevention or amelioration of a condition associated with SMN deficiency, eg spinal muscular atrophy (SMA). 18. A method of treating, preventing or ameliorating a condition associated with SMN deficiency, such as spinal muscular atrophy (SMA), comprising administering to a subject in need thereof an effective amount of a composition according to any one of the preceding claims. 19. The method of claim 18, wherein the composition is administered at a dose of from about 0.625 mg/kg to about 3.125 mg/kg of branaplam, in free form or in pharmaceutically acceptable salt form, based on the weight of the subject.