Amlodipine formulations
Provided herein are stable amlodipine liquid formulations. Also provided herein are methods of using amlodipine 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 a subject a suspension comprising particles comprising amlodipine benzoate and having a median particle diameter D50 value of between 5 μm and 40 μm as measured by a particle size analyzer, wherein the suspension is made by mixing amlodipine besylate and sodium benzoate in an aqueous mixture between 1 minute and 1 hour, thereby forming the suspension comprising particles comprising amlodipine benzoate.
2. The method of claim 1 , wherein the particles have the D50 value between 10 μm and 20 μm.
3. The method of claim 1 , wherein the concentration of amlodipine besylate is between 12 mg/ml and 20 mg/ml.
4. The method of claim 1 , wherein the concentration of sodium benzoate is between 40 mg/ml and 70 mg/ml.
5. The method of claim 1 , wherein the mixing comprises ultrasonic agitation.
6. The method of claim 1 , wherein the mixing occurs by a mixing device, wherein the mixing device is a homogenizer or a blender.
7. The method of claim 1 , wherein the duration of the mixing is between 1 minute and 30 minutes.
8. The method of claim 1 , wherein the final concentration of amlodipine benzoate in the suspension is equivalent to about 1.0 mg/ml of amlodipine free base.
9. The method of claim 1 , wherein the suspension further comprises at least one of the following: a buffer, a preservative, a sweetening agent, a suspension agent, an antifoaming agent, and a flavoring agent.
10. The method of claim 9 , wherein the suspension agent is selected from the group consisting of silicon dioxide, hydroxypropyl methylcellulose, methyl cellulose, microcrystalline cellulose, polyvinylpyrrolidone, xanthan gum, magnesium aluminum silicate, crosslinked polyacrylic acid polymers, and any combination thereof.
11. The method of claim 9 , wherein the suspension agent is a combination of silicon dioxide and hydroxypropyl methylcellulose.
12. The method of claim 9 , wherein the amount of preservative is from about 0.1 mg/ml to about 5.0 mg/ml.
13. The method of claim 1 , wherein the suspension is stable at about 25±5° C. for at least 6 months.
14. The method of claim 1 , wherein the suspension is stable at about 5±5° C. for at least 6 months.
15. The method of claim 1 , wherein the hypertension is primary or secondary hypertension.
16. A method of treating coronary artery disease (CAD) in a subject comprising administering to a subject a suspension comprising particles comprising amlodipine benzoate and having a median particle diameter D50 value of between 5 μm and 40 μm as measured by a particle size analyzer, wherein the suspension is made by mixing amlodipine besylate and sodium benzoate in an aqueous mixture between 1 minute and 1 hour, thereby forming the suspension comprising particles comprising amlodipine benzoate.
17. The method of claim 16 , wherein the CAD is chronic stable angina, vasospastic angina, or angiographically documented coronary artery disease.
18. The method of claim 16 , wherein the angiographically documented coronary artery disease is in patients without heart failure or an ejection fraction of less than 40%.
19. The method of claim 16 , wherein the suspension is further administered in combination with an additional anti-anginal agent.
20. The method of claim 16 , wherein the particles have the D50 value between 10 μm and 20 μm.
21. The method of claim 16 , wherein the duration of the mixing is between 1 minute and 30 minutes.
22. The method of claim 16 , wherein the final concentration of amlodipine benzoate in the suspension is equivalent to about 1.0 mg/ml of amlodipine free base.
23. The method of claim 16 , wherein the suspension further comprises at least one buffer, a preservative, a sweetening agent, a suspension agent, an antifoaming agent, and a flavoring agent.