Claims for Patent: 11,484,498

Summary for Patent: 11,484,498

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:	US17/345,943
Patent Claims:	1. A suspension comprising particles comprising amlodipine benzoate and having a median diameter D50 value of between 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 agitation thereby forming a second mixture comprising amlodipine benzoate, wherein the agitation comprises mixing for a period between 1 minute and 1 hour. 2. The suspension of claim 1, wherein the said particles have the D50 value of between 10 μm and 20 μm. 3. The suspension 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 suspension of claim 1, wherein the aqueous mixture of step (i) further comprises a surfactant, and wherein the surfactant comprises polysorbate 80. 5. The suspension of claim 1, wherein the concentration of amlodipine besylate is between 12 mg/ml and 20 mg/ml. 6. The suspension of claim 1, wherein the concentration of sodium benzoate is between 40 mg/ml and 70 mg/ml. 7. The suspension of claim 1, wherein the first mixture is subjected to the agitation of a mixing device. 8. The suspension of claim 7, wherein the mixing device is a homogenizer or a blender. 9. The suspension of claim 1, wherein the agitation comprises stirring with a magnetic stir bar. 10. The suspension of claim 1, wherein the duration of the agitation is between 1 minute and 30 minutes. 11. The suspension of claim 4, wherein the amount of the surfactant is about 0.1 mg/ml to about 2 mg/ml. 12. The suspension of claim 1, wherein step (iii) further comprises adding the second mixture comprising amlodipine benzoate to a third mixture comprising at least one of a buffer, a preservative, a sweetening agent, a suspension agent, an antifoaming agent, water, and a flavoring agent. 13. The suspension of claim 12, wherein the amount of the preservative is about 0.1 mg/ml to about 5.0 mg/ml. 14. The suspension of claim 12, wherein the buffer comprises a citrate buffer. 15. The suspension of claim 14, wherein the citrate buffer concentration is about 3 mM. 16. The suspension of claim 12, 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 any combinations thereof. 17. The suspension of claim 12, wherein the suspension agent is a combination of silicon dioxide and hydroxypropyl methylcellulose. 18. The suspension of claim 12, wherein the antifoaming agent is simethicone. 19. The suspension of claim 1, wherein the final concentration of amlodipine benzoate in the suspension corresponds to about 1.0 mg/ml 0.8 mg/ml of amlodipine free base. 20. The suspension of claim 1, wherein the suspension is stable at about 25±5° C. for at least 6 months. 21. The suspension of claim 1, wherein the suspension is stable at about 5±5° C. for at least 12 months. 22. A suspension comprising particles comprising amlodipine benzoate having a median diameter of D50 value between 5 μm and 40 μm as measured by a light scattering particle size analyzer, the suspension made by a process comprising: (i) providing an aqueous mixture comprising pharmaceutically acceptable salt of amlodipine selected from the group consisting of amlodipine besylate, amlodipine nicotinate, amlodipine pamoate, amlodipine terephthalate, amlodipine 1-hydroxy-2-naphthoic acid salt, amlodipine (1S)-(+)-10-camphorsulfonic acid salt, amlodipine 1,5-naphthalene disulfonic acid salt, or amlodipine naphthalene sulfonate; (ii) adding sodium benzoate to the aqueous mixture to form a first mixture; and (iii) subjecting the first mixture to agitation thereby forming a second mixture comprising amlodipine benzoate, wherein the agitation comprises mixing for a period between 1 minute and 30 minutes; (iv) subjecting the second mixture to a third mixture, wherein the third mixture comprises a citrate buffer, sodium benzoate, silicon dioxide, hydroxypropyl methylcellulose, simethicone, a surfactant, and water; thereby producing the suspension; wherein the suspension comprises: (i) amlodipine benzoate in an amount corresponding to about 0.8 mg/ml to about 1.2 mg/ml of amlodipine free base; (ii) citrate buffer in an amount between 1 mM and 5 mM; (iii) about 0.1 mg/ml to about 5.0 mg/ml of sodium benzoate; (iv) about 0.1 mg/ml to about 1.0 mg/ml of silicon dioxide; (v) about 3 mg/ml to about 10 mg/ml of hydroxypropyl methylcellulose; (vi) about 0.1 mg/ml to about 1.0 mg/ml of simethicone; (vii) about 0.1 mg/ml to about 2 mg/ml of the surfactant and (viii) water. 23. A suspension comprising particles comprising amlodipine benzoate having a median diameter of D50 value between 5 μm and 40 μm as measured by a light scattering particle size analyzer, the suspension made by a process comprising: (i) providing an aqueous mixture comprising pharmaceutically acceptable salt of amlodipine selected from the group consisting of amlodipine besylate, amlodipine nicotinate, amlodipine pamoate, amlodipine terephthalate, amlodipine 1-hydroxy-2-naphthoic acid salt, amlodipine (1S)-(+)-10-camphorsulfonic acid salt, amlodipine 1,5-naphthalene disulfonic acid salt, or amlodipine naphthalene sulfonate; (ii) adding sodium benzoate to the aqueous mixture to form a first mixture; and (iii) subjecting the first mixture to agitation thereby forming a second mixture comprising amlodipine benzoate, wherein the agitation comprises mixing for a period between 1 minute and 30 minutes, (iv) subjecting the second mixture to a third mixture, wherein the third mixture comprises a citrate buffer, sodium benzoate, silicon dioxide, hydroxypropyl methylcellulose, simethicone, a surfactant, and water; thereby producing the suspension; wherein the suspension comprises: (i) amlodipine benzoate in an amount corresponding to about 1.0 mg/ml of amlodipine free base; (ii) about 3 mM of the citrate buffer; (iii) about 0.1 mg/ml to 5.0 mg/ml of sodium benzoate; (iv) about 0.5 mg/ml of silicon dioxide; (v) about 7.5 mg/ml of hydroxypropyl methylcellulose; (vi) about 0.15 mg/ml of simethicone; (vii) 1.0 mg/ml of the surfactant; and (viii) water; and wherein the suspension is stable at 5±5° C. for at least 12 months. 24. The suspension of claim 23, wherein the surfactant comprises polysorbate 80. 25. The suspension of claim 1, wherein the agitation comprises stirring for at least 10 minutes. 26. The suspension of claim 22, wherein the surfactant comprises polysorbate 80.