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 kit, comprising:
(1) a pharmaceutical composition that comprises:
(a) a salt of flecainide,
(b) a cyclodextrin, and
(c) an acid;
(2) a receptacle containing said pharmaceutical composition; and
(3) instructions for use of a nebulizer to inhalationally administer a dose of said pharmaceutical composition in aerosol to a subject, wherein said dose contains from about 50 mg to about 250 mg of said salt of flecainide, and said aerosol of said pharmaceutical composition has droplets that have a mass median aerodynamic diameter of less than 10 μm; and
wherein said pharmaceutical composition is in the form of a liquid solution that has:
(i) said salt of flecainide at a concentration of from about 65 mg/mL to about 95 mg/mL;
(ii) said cyclodextrin at a concentration of from about 10% (w/v) to about 30% (w/v) of said liquid solution;
(iii) said acid at a concentration of from about 2 mM to about 10 mM; and
(iv) a pH of from about 5.5 to about 6.5 when said pH is measured at room temperature.
2. The kit of claim 1 , wherein said concentration of said salt of flecainide is from about 70 mg/mL to about 80 mg/mL.
3. The kit of claim 1 , wherein said concentration of said salt of flecainide is about 75 mg/mL.
4. The kit 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.
5. The kit of claim 1 , wherein said salt of flecainide comprises flecainide acetate.
6. The kit of claim 1 , wherein said acid is selected from the group consisting of: acetic acid, citric acid, nitric acid, hydrochloric acid, ascorbic acid, lactic acid, sulfuric acid, maleic acid, tartaric acid, phosphoric acid, aconitic acid, adipic acid, benzoic acid, caprylic acid, cholic acid, formic acid, glutamic acid, lactic acid, propionic acid, sorbic acid, stearic acid, and succinic acid.
7. The kit of claim 1 , wherein said acid comprises acetic acid.
8. The kit of claim 1 , wherein said acid comprises citric acid.
9. The kit of claim 1 , wherein said concentration of said acid is about 5 mM.
10. The kit of claim 1 , wherein said pH of said liquid solution is about 5.9 when measured at room temperature.
11. The kit 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.
12. The kit of claim 1 , wherein said cyclodextrin comprises hydroxypropyl-β-cyclodextrin.
13. The kit of claim 1 , wherein said concentration of said cyclodextrin is from about 15% (w/v) to about 25% (w/v) of said liquid solution.
14. The kit of claim 1 , wherein said concentration of said cyclodextrin is about 20% (w/v) of said liquid solution.
15. The kit of claim 1 , wherein said pharmaceutical composition further comprises an artificial sweetener.
16. The kit of claim 1 , wherein said dose contains from about 150 mg to about 250 mg of said salt of flecainide.
17. The kit of claim 16 , wherein said dose contains about 200 mg of said salt of flecainide.
18. The kit of claim 1 , further comprising a nebulizer selected from the group consisting of: a breath-actuated jet nebulizer, a vibrating mesh nebulizer, and an ultrasonic nebulizer.
19. The kit of claim 1 , wherein said pharmaceutical composition is formulated for administration via a breath-actuated jet nebulizer, a vibrating mesh nebulizer, or an ultrasonic nebulizer.
20. The kit of claim 16 , wherein said dose contains about 175 mg of said salt of flecainide.
21. The kit 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.