Antiarrhythmic formulation
Pharmaceutical compositions comprising an antiarrhythmic agent for treatment of a heart condition via inhalation. Methods of treating a heart condition include administering by inhalation an effective amount of at least one antiarrhythmic pharmaceutical agent to a patient in need thereof. Nebulized drug product and kits are also disclosed.
1. A pharmaceutical composition, comprising:
(1) a therapeutically effective amount of a salt of flecainide,
(2) a cyclodextrin, and
(3) an acid,
wherein said pharmaceutical composition is in the form of a liquid solution that has said salt of flecainide at a concentration above 60 mg/mL, said cyclodextrin at a concentration of from about 5% (w/v) to about 50% (w/v) of said liquid solution, said acid at a concentration of 2 mM to 10 mM, and a pH above 5.5 when measured at room temperature.
2. The pharmaceutical composition of claim 1 , wherein said concentration of said cyclodextrin is from about 15% (w/v) to about 25% (w/v) of said liquid solution.
3. The pharmaceutical composition of claim 1 , wherein said concentration of said cyclodextrin is about 20% (w/v) of said liquid solution.
4. The pharmaceutical composition of claim 1 , wherein said cyclodextrin is selected from the group consisting of: α-cyclodextrin, β-cyclodextrin, γ-cyclodextrin, hydroxypropyl-β-cyclodextrin, hydroxyethyl-β-cyclodextrin, hydroxypropyl-γ-cyclodextrin, hydroxyethyl-γ-cyclodextrin, dihydroxypropyl-β-cyclodextrin, glucosyl-α-cyclodextrin, glucosyl-β-cyclodextrin, diglucosyl-β-cyclodextrin, maltosyl-α-cyclodextrin, maltosyl-β-cyclodextrin, maltosyl-γ-cyclodextrin, maltotriosyl-β-cyclodextrin, maltotriosyl-γ-cyclodextrin, dimaltosyl-β-cyclodextrin, succinyl-β-cyclodextrin, 6A-amino-6A-deoxy-N-(3-hydroxypropyl)-β-cyclodextrin, sulfobutylether-β-cyclodextrin, sulfobutylether-γ-cyclodextrin, sulfoalkylether-β-cyclodextrins, and sulfoalkylether-γ-cyclodextrins.
5. The pharmaceutical composition of claim 1 , wherein said cyclodextrin comprises hydroxypropyl-β-cyclodextrin.
6. The pharmaceutical composition of claim 1 , wherein said concentration of said salt of flecainide is up to 200 mg/mL.
7. The pharmaceutical composition of claim 1 , wherein said concentration of said salt of flecainide is from about 65 mg/mL to about 95 mg/mL.
8. The pharmaceutical composition of claim 1 , wherein said concentration of said salt of flecainide is about 75 mg/mL.
9. The pharmaceutical composition of claim 1 , wherein said salt of flecainide is selected from the group consisting of: flecainide acetate, flecainide hydrochloride, flecainide citrate, flecainide phosphate, and flecainide nitrate.
10. The pharmaceutical composition of claim 1 , wherein said salt of flecainide comprises flecainide acetate.
11. The pharmaceutical composition of claim 1 , wherein said acid is selected from the group consisting of: acetic acid, citric acid, nitric acid, hydrochloric acid, sulfuric acid, maleic acid, tartaric acid, phosphoric acid, aconitic acid, adipic acid, ascorbic acid, benzoic acid, caprylic acid, cholic acid, formic acid, glutamic acid, lactic acid, propionic acid, sorbic acid, stearic acid, and succinic acid.
12. The pharmaceutical composition of claim 1 , wherein said acid comprises acetic acid.
13. The pharmaceutical composition of claim 1 , wherein said acid comprises citric acid.
14. The pharmaceutical composition of claim 1 , wherein said concentration of said acid is about 5 mM.
15. The kit of claim 1 , wherein said pH of said liquid solution is about 5.9 when measured at room temperature.
16. The pharmaceutical composition of claim 1 , wherein said pharmaceutical composition further comprises a sweetener.
17. The pharmaceutical composition of claim 16 , wherein said sweetener is selected from the group consisting of acesulfame potassium, aspartame, cyclamate, mogrosides, saccharin, stevia , sucralose, neotame, mannitol, sorbitol, xylitol, lactitol, isomalt, maltitol, and pharmaceutically acceptable salts thereof.
18. The pharmaceutical composition of claim 1 , wherein said pharmaceutical composition is formulated for administration via inhalation.
19. A unit dose of a pharmaceutical composition that comprises: a salt of flecainide, a cyclodextrin, and an acid,
wherein said pharmaceutical composition is in the form of a liquid solution that has said salt of flecainide at a concentration above 60 mg/mL, said cyclodextrin at a concentration of from about 5% (w/v) to about 50% (w/v) of said liquid solution, said acid at a concentration of 2 mM to 10 mM, and a pH above 5.5 when measured at room temperature, and
wherein said unit dose comprises from about 50 mg to about 350 mg of said salt of flecainide.
20. The unit dose of claim 19 , comprising from about 250 mg to about 350 mg of said salt of flecainide.
21. The unit dose of claim 19 , comprising from about 100 mg to about 250 mg of said salt of flecainide.
22. The unit dose of claim 20 , wherein:
(i) said salt of flecainide comprises flecainide acetate, and said concentration of said salt of flecainide is about 75 mg/mL;
(ii) said acid comprises acetic acid; and
(iii) said cyclodextrin comprises hydroxypropyl-β-cyclodextrin, and said concentration of said cyclodextrin is about 20% (w/v) of said liquid solution.
23. The unit dose of claim 21 , wherein:
(i) said salt of flecainide comprises flecainide acetate, and said concentration of said salt of flecainide is about 75 mg/mL;
(ii) said acid comprises acetic acid; and
(iii) said cyclodextrin comprises hydroxypropyl-β-cyclodextrin, and said concentration of said cyclodextrin is about 20% (w/v) of said liquid solution.
24. The unit dose of claim 19 , wherein said concentration of salt of flecainide is from about 65 mg/mL to about 95 mg/mL.
25. The unit dose of claim 24 , wherein said salt of flecainide comprises flecainide acetate.
26. The unit dose of claim 25 , wherein said cyclodextrin comprises hydroxypropyl-β-cyclodextrin, and said concentration of said cyclodextrin is from about 15% (w/v) to about 25% (w/v) of said liquid solution.
27. The unit dose of claim 26 , wherein said pH is about 5.8 to about 6.2 when measured at room temperature.
28. The composition of claim 1 , wherein:
(a) said salt of flecainide comprises flecainide acetate, and said concentration of said salt of flecainide is about 75 mg/mL;
(b) said acid comprises acetic acid; and
(c) said cyclodextrin comprises hydroxypropyl-β-cyclodextrin, and said concentration of said cyclodextrin is about 20% (w/v) of said liquid solution.