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 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 suspension of claim 1 , wherein the particles have the D50 value of between 10 μm and 20 μm.
3. The suspension of claim 1 , wherein the particles further have a D90 value of between 20 μm and 60 μm as measured by a particle size analyzer, and wherein the D90 value refers to a particle diameter, wherein 10% of the volume of the sampled particles have a diameter large than, and 90% of the volume of the sampled particles have a diameter smaller than the D90 value.
4. The suspension of claim 1 , wherein the concentration of amlodipine besylate is between 12 mg/ml and 20 mg/ml.
5. The suspension of claim 1 , wherein the concentration of sodium benzoate is between 40 mg/ml and 70 mg/ml.
6. The suspension of claim 1 , wherein the mixing comprises ultrasonic agitation.
7. The suspension of claim 6 , wherein the ultrasonic agitation has a frequency of between 20 kHz and 100 kHz.
8. The suspension of claim 1 , wherein the mixing occurs by a mixing device, wherein the mixing device is a homogenizer or a blender.
9. The suspension of claim 1 , wherein the duration of the mixing is between 1 minute and 30 minutes.
10. The suspension 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.
11. The suspension of claim 1 , wherein the suspension further comprises at least one buffer, a preservative, a sweetening agent, a suspension agent, an antifoaming agent, and a flavoring agent.
12. The suspension of claim 11 , 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.
13. The suspension of claim 11 , wherein the suspension agent is a combination of silicon dioxide and hydroxypropyl methylcellulose.
14. The suspension of claim 11 , wherein the amount of preservative is from about 0.1 mg/ml to about 5.0 mg/ml.
15. The suspension of claim 11 , wherein the buffer comprises a citrate buffer.
16. The suspension of claim 15 , wherein the citrate buffer concentration is about 3 mM.
17. The suspension of claim 11 , wherein the antifoaming agent is simethicone.
18. The suspension of claim 1 , wherein the suspension is stable at about 25±5° C. for at least 6 months.
19. The suspension of claim 1 , wherein the suspension is stable at about 5±5° C. for at least 6 months.