Amlodipine formulations
View Patent ↗Provided herein are stable amlodipine oral liquid formulations. Also provided herein are methods of using amlodipine oral liquid formulations for the treatment of certain diseases including hypertension and Coronary Artery Disease (CAD).
1. A method of treating hypertension in a subject comprising administering to the subject an oral liquid formulation, wherein the oral liquid formulation comprises:
(i) amlodipine benzoate in an amount corresponding to 1.0 mg/ml amlodipine freebase;
(ii) 3 mM of a citrate buffer;
(iii) 0.2 mg/ml to about 10 mg/ml of sodium benzoate;
(iv) 0.5 mg/ml of silicon dioxide;
(v) 7.5 mg/ml of hydroxypropyl methylcellulose;
(vi) 0.15 mg/ml simethicone;
(vii) 1.0 mg/ml of polysorbate 80; and
(viii) water;
wherein the pH of the formulation is between 4 and 6, and wherein the formulation is stable at 5±5° C. for at least 12 months; and wherein the stable oral liquid formulation has 95% w/w or greater of the initial amlodipine amount and 5% w/w or less total impurities or related substances at the end of the given storage period.
2. The method of claim 1 , wherein the amlodipine benzoate is formed in situ.
3. The method of claim 1 , wherein the amlodipine benzoate is formed by a reaction of a pharmaceutically acceptable salt of amlodipine that is more soluble in aqueous media than amlodipine benzoate with a molar excess of sodium benzoate.
4. The method of claim 3 , wherein the salt of amlodipine that is more soluble in aqueous media than amlodipine benzoate is selected from amlodipine besylate, amlodipine tosylate, amlodipine mesylate, amlodipine succinate, amlodipine salicylate, amlodipine maleate, amlodipine acetate, and amlodipine hydrochloride.
5. The method of claim 1 , wherein the amlodipine benzoate is formed by the reaction of amlodipine besylate with a molar excess of sodium benzoate.
6. The method of claim 1 wherein the formulation further comprises a flavoring agent.
7. The method of claim 1 , wherein the formulation further comprises a sweetener.
8. The method of claim 1 , wherein the formulation is in the form of a suspension.
9. The method of claim 1 , wherein the pH is between about 5 and about 6.
10. The method of claim 1 , wherein the formulation is stable at 5±5° C. for at least 24 months.
11. The method of claim 1 , wherein the hypertension is primary or secondary hypertension.
12. The method of claim 1 , wherein the subject has blood pressure values greater than or equal to 140/90 mm Hg.
13. The method of claim 1 , wherein the formulation is administered to the subject in a fasted state or a fed state.
14. The method of claim 1 , wherein the subject is an elderly.
15. The method of claim 1 , wherein the subject is an adult.
16. The method of claim 1 , wherein the subject is a child.
17. The method of claim 1 , wherein the formulation is further administered in combination with an agent selected from the group consisting of diuretics, beta blockers, alpha blockers, mixed alpha and beta blockers, calcium channel blockers, angiotensin II receptor antagonists, ACE inhibitors, aldosterone antagonists, and alpha-2 agonists.
18. The method of claim 1 , wherein the formulation is stable at 25±5° C. for at least 6 months.
19. The method of claim 1 , wherein the formulation is stable at 25±5° C. for at least 12 months.