LIQUID RIZATRIPTAN COMPOSITIONS
The present invention is directed to liquid rizatriptan compositions. The present invention is further directed to methods of treating migraines comprising administering a liquid rizatriptan composition to a subject in need thereof.
1 . A liquid rizatriptan composition comprising rizatriptan or a salt thereof and a solvent selected from the group consisting of water, ethanol, propylene glycol, polyethylene glycol 400 and a combination thereof.
2 . The composition of claim 1 , further comprising one or more agents selected from the group consisting of a solubilizing agent, a stabilizer, a permeation enhancer, a preservative, a pH modifier, a sweetener and a flavoring agent.
3 . The composition of claim 2 , wherein the one or more agents comprises a solubilizing agent selected from a polysorbate and an inclusion complex forming agent.
4 . The composition of claim 2 , wherein the one or more agents comprises a stabilizer selected from the group consisting of D,L-alpha tocopherol, butylated hydroxytoluene, methionine, ascorbyl palmitate, ascorbic acid, butylated hydroxyanisole, citric acid, ethylenediamine tetra acetic acid, sodium bisulfate, tert-butylhydroquinone, propyl gallate and a combination thereof.
5 . The composition of claim 2 , wherein the one or more agents comprises a permeation enhancer selected from the group consisting of octanoic acid, oleic acid, polysorbate 80, menthol, EDTA, sodium edetate, cetylpyridinium chloride, sodium lauryl sulfate, citric acid, sodium desoxycholate, sodium deoxyglycolate, glyceryl oleate, L-lysine and a combination thereof.
6 . The composition of claim 2 , wherein the one or more agents comprises a preservative selected form the group consisting of benzalkonium chloride, butyl paraben, methyl paraben, ethyl paraben, propyl paraben, sodium benzoate, benzoic acid and a combination thereof
7 . The composition of claim 1 , wherein the composition has a pH from about 3 to about 11.
8 . The composition of claim 2 , wherein the one or more agents comprises a pH modifier selected from the group consisting of dilute hydrochloric acid, citric acid, fumaric acid, lactic acid, dilute sodium hydroxide, sodium citrate, sodium bicarbonate, sodium carbonate, ammonium carbonate and a combination thereof.
9 . A liquid rizatriptan composition comprising:
from about 2% to about 15.73% w/w rizatriptan; and
a solvent selected from the group consisting of from about 1% to about 97% w/w water, from about 10% to about 60% w/w ethanol, from about 1% to about 50% w/w propylene glycol, from about 1% to about 50% polyethylene glycol 400 and a combination thereof,
wherein w/w denotes weight by total weight of the formulation.
10 . The composition of claim 9 , further comprising from about 10% to about 50% w/w of a solubilizing agent selected from the group consisting of a polysorbate and a cyclodextrin.
11 . The composition of claim 10 , wherein the cyclodextrin is selected from the group consisting of hydroxypropyl beta cyclodextrin and sulfobutylether beta cyclodextrin.
12 . The composition of claim 9 , further comprising from about 0.002% to about 0.2% w/w of a stabilizer.
13 . The composition of claim 9 , further comprising from about 0.02% to about 7.8% w/w of a permeation enhancer.
14 . The composition of claim 9 , further comprising from about 0.005% to about 0.2% w/w of a preservative.
15 . A liquid rizatriptan composition comprising:
about 7.414% w/w rizatriptan benzoate;
about 20% w/w ethanol; and
about 72.394% w/w water,
wherein w/w denotes weight by total weight of the composition.
16 . The composition of claim 15 , further comprising about 0.002% w/w butylated hydroxytoluene, about 0.02% w/w butylated hydroxy anisole, about 0.05% w/w edetate disodium and about 0.02% w/w benzalkonium chloride.
17 . The composition of claim 15 , wherein the composition provides a pharmacokinetic parameter following nasal administration to a beagle dog selected from the group consisting of a Cmax from about 100 to about 650 nanograms per milliliter, a Tmax from about 3 to about 20 minutes, an AUC from 3,500 to about 17,000 nanogram minutes per milliliter and a combination thereof.
18 . A method of treating migraines comprising administering to a subject in need thereof an effective amount of a composition of claim 1 .
19 . The method of claim 1 , wherein the composition is administered nasally via a spray pump at an amount from about 50 to about 200 microliters.
20 . A liquid rizatriptan composition comprising:
about 14.534% w/w rizatriptan benzoate;
about 50% w/w ethanol; and
about 29.346% w/w water,
wherein w/w denotes weight by total weight of the composition.
21 . The composition of claim 20 , further comprising about 0.1% w/w Vitamin E, about 0.02% w/w edetate disodium, dihydrate, about 0.5% w/w menthol and about 0.5% w/w sucralose.