Claims for Patent: 11,471,409

Summary for Patent: 11,471,409

Title:	Amlodipine formulations
Abstract:	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).
Inventor(s):	Scott BRAUER, Gerold L. Mosher
Assignee:	Azurity Pharmaceuticals Inc
Application Number:	US17/067,396
Patent Claims:	1. A method of treating hypertension in a subject comprising administering to the subject a suspension comprising particles comprising amlodipine benzoate and having a median diameter D50 value of between about 5 μm and about 40 μm as measured by a light scattering particle size analyzer, and the said suspension is made by a process comprising: (i) providing an aqueous mixture comprising amlodipine besylate; (ii) adding sodium benzoate to the aqueous mixture to form a first mixture; and (iii) subjecting the first mixture to ultrasonic agitation at a frequency of between 20 kHz and 100 kHz, thereby forming a second mixture comprising amlodipine benzoate. 2. The method of claim 1, wherein the said particles have the D50 value of between 10 μm and 20 μm. 3. The method of claim 1, wherein the said particles have a D90 value of between 20 μm and 60 μm, and wherein the D90 value refers to a particle diameter, wherein 10% of the volume of the sampled particles have a diameter larger than, and 90% of the volume of the sampled particles have a diameter smaller than said D90 value. 4. The method of claim 1, wherein the aqueous mixture of step (i) further comprises a surfactant, wherein the surfactant is polysorbate 80. 5. The method of claim 4, wherein the amount of the surfactant is from about 0.1 mg/ml to about 2 mg/ml. 6. The method of claim 1, wherein the concentration of amlodipine besylate is between 12 mg/ml and 20 mg/ml in the aqueous mixture of step (i). 7. The method of claim 1, wherein the concentration of sodium benzoate is between 40 mg/ml and 70 mg/ml in the first mixture of step (ii). 8. The method of claim 1, wherein the duration of the ultrasonic agitation in step (iii) is between 1 minute and 1 hour. 9. The method of claim 1, wherein the aqueous mixture of step (i) does not comprise any solvent other than water. 10. The method of claim 1, wherein the process further comprises adding the second mixture comprising amlodipine benzoate to a third mixture comprising at least one component selected from a buffer, a preservative, a sweetening agent, a suspension agent, an antifoaming agent, water, and a flavoring agent. 11. The method of claim 10, wherein the suspension agent is selected from the group consisting of silicon dioxide, hydroxypropyl methylcellulose, methylcellulose, microcrystalline cellulose, polyvinylpyrrolidone, xanthan gum, magnesium aluminum silicate, crosslinked polyacrylic acid polymers, and combinations thereof. 12. The method of claim 10, wherein the suspension agent is a combination of silicon dioxide and hydroxypropyl methylcellulose. 13. The method of claim 1, wherein a final concentration of amlodipine benzoate in the suspension is equivalent to about 1.0 mg/ml of amlodipine free base. 14. The method of claim 1, wherein the hypertension is primary or secondary hypertension. 15. The method of claim 1, wherein the subject has a systolic blood pressure greater than or equal to 140 mm Hg and a diastolic blood pressure greater than or equal to 90 mm Hg. 16. The method of claim 1, wherein the subject is a human of the age of 60 years or older. 17. The method of claim 1, wherein the subject is a human of the age of 12 years or younger. 18. The method of claim 1, wherein the suspension 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, angiotensin-converting enzyme inhibitors, aldosterone antagonists, and alpha-2 agonists. 19. A method of treating coronary artery disease (CAD) in a subject comprising administering to the subject a suspension comprising particles comprising amlodipine benzoate and having a median diameter D50 value of between about 5 μm and 40 μm as measured by a light scattering particle size analyzer, and the said suspension is made by a process comprising: (i) providing an aqueous mixture comprising amlodipine besylate; (ii) adding sodium benzoate to the aqueous mixture to form a first mixture; and (iii) subjecting the first mixture to ultrasonic agitation at a frequency of between 20 kHz and 100 kHz, thereby forming a second mixture comprising amlodipine benzoate. 20. The method of claim 19, wherein the said particles have the D50 value of between 10 μm and 20 μm. 21. The method of claim 19, wherein the said particles have a D90 value of between 20 μm and about 60 μm, and wherein the D90 value refers to a particle diameter, wherein 10% of the volume of the sampled particles have a diameter larger than, and 90% of the volume of the sampled particles have a diameter smaller than said D90 value. 22. The method of claim 19, wherein the aqueous mixture of step (i) further comprises a surfactant, wherein the surfactant is polysorbate 80. 23. The method of claim 19, wherein a final concentration of amlodipine benzoate in the suspension is equivalent to about 1.0 mg/ml of amlodipine free base. 24. The method of claim 19, wherein the concentration of amlodipine besylate is between about 12 mg/ml and 20 mg/ml in the aqueous mixture of step (i). 25. The method of claim 19, wherein the duration of the ultrasonic agitation in step (iii) is between 1 minute and 1 hour. 26. The method of claim 19, wherein the CAD is chronic stable angina, vasospastic angina, or angiographically documented coronary artery disease. 27. The method of claim 26, wherein the angiographically documented coronary artery disease is in patients without heart failure or an ejection fraction of less than 40%. 28. The method of claim 19, wherein the suspension is further administered in combination with an additional anti-anginal agent. 29. The method of claim 19, wherein the subject is a human of the age of 12 years or younger.