FORMULATIONS FOR CGRP RECEPTOR ANTAGONISTS
The instant invention relates to liquid pharmaceutical compositions containing CGRP receptor antagonists. The CGRP receptor antagonist liquid pharmaceutical compositions of the instant invention are alcohol-free, low volume liquid pharmaceutical compositions that can be taken without water for the treatment of migraine headache.
1 . A liquid pharmaceutical composition comprising (S)—N-((3S,5S,6R)-6-methyl-2-oxo-5-phenyl-1-(2,2,2-trifluoroethyl)piperidine-3-yl)-2′-oxo-1′,2′,5,7-tetrahydrospiro[cyclopenta[b]pyridine-6,3′-pyrrolo[2,3-b]pyridine]-3-carboxamide, or a pharmaceutically acceptable salt thereof present in an amount of 0.01% to 3.0% by weight of the composition, and a pharmaceutically acceptable carrier comprising at least one water soluble surfactant present in the amount of about 0.1% to 15% by weight of the composition selected from vitamin E-tocopherol polyethylene glycol succinate and poloxamer, wherein the volume of the carrier is less than 10 mL, said composition has a viscosity at 25° C. of less than about 0.065 Pa·sec,
and wherein, when said composition is diluted up to ⅕ of its original concentration with artificial saliva it does not precipitate said API within 30 minutes.
2 . The liquid pharmaceutical composition according to claim 1 comprising (S)—N-((3S,5S,6R)-6-methyl-2-oxo-5-phenyl-1-(2,2,2-trifluoroethyl)piperidine-3-yl)-2′-oxo-1′,2′,5,7-tetrahydrospiro[cyclopenta[b]pyridine-6,3′-pyrrolo[2,3-b]pyridine]-3-carboxamide trihydrate.
3 . (canceled)
4 . The liquid pharmaceutical composition according to claim 1 , wherein the carrier comprises water, glycols, glycol esters or a combination thereof.
5 . The liquid pharmaceutical composition according to claim 4 , comprising glycols selected from the group consisting of propylene glycol and PEG; and glycol ester selected from the group consisting of glycerol esters, propylene glycol esters of organic acids or mixtures thereof.
6 . The liquid pharmaceutical composition according to claim 5 , wherein glycol is selected from the group consisting of propylene glycol, polyethylene glycol 400, glycerol and mixtures thereof.
7 . The liquid pharmaceutical composition according to claim 5 , wherein glycol ester is selected from the group consisting of triacetin, triethyl citrate and mixtures thereof.
8 .- 10 . (canceled)
11 . The liquid pharmaceutical composition according to claim 10 , wherein the water soluble surfactant is present in an amount of 2.5% to 10% by weight of the composition.
12 .- 13 . (canceled)
14 . The liquid pharmaceutical composition according to claim 1 , wherein (S)—N((3 S,5S,6R)-6-methyl-2-oxo-5-phenyl-1-(2,2,2-trifluoroethyl)piperidine-3-yl)-2′-oxo-1′,2′,5,7-tetrahydrospiro[cyclopenta[b]pyridine-6,3′-pyrrolo[2,3-b]pyridine]-3-carboxamide or a salt thereof is present in an amount of 0.25% to 2.0% by weight of the composition.
15 . The liquid pharmaceutical composition according to claim 1 , wherein the volume of carrier is less than 5 mL.
16 . The liquid pharmaceutical composition according to claim 1 , further comprising one or more pharmaceutically acceptable excipients selected from the group consisting of anti-nucleating polymers, antioxidants, chelating agents, souring agents, sodium chloride, colors, sweeteners and flavors.
17 . The liquid pharmaceutical composition according to claim 1 comprising propylene glycol, polyethylene glycol 400, Water, vitamin E-tocopherol polyethylene glycol succinate, Povidone, Sucralose, Menthol, and a mint or peppermint flavor.
18 . The liquid pharmaceutical composition according to claim 17 , which further comprises a souring agent.
19 . A method of treating migraine headache by administering a liquid pharmaceutical composition according to claim 1 .
20 . A method of treating migraine headache by administering a liquid pharmaceutical composition according to claim 17 .