Claims for Patent: 10,786,482

Summary for Patent: 10,786,482

Title:	Enalapril formulations
Abstract:	Provided herein are stable enalapril oral liquid formulations. Also provided herein are methods of using enalapril oral liquid formulations for the treatment of certain diseases including hypertension, heart failure and asymptomatic left ventricular dysfunction.
Inventor(s):	Gerold L. Mosher, David W. Miles
Assignee:	Azurity Pharmaceuticals Inc
Application Number:	US16/177,159
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 10,786,482
Patent Claims:	1. An oral liquid formulation, comprising: (i) about 0.6 to about 1.2 mg/ml enalapril or a pharmaceutically acceptable salt or solvate thereof; (ii) a buffer comprising a mixture of citric acid and sodium citrate, wherein the buffer is present at a concentration between about 5 mM and about 20 mM in the oral liquid formulation; (iii) about 1 mg/ml sodium benzoate; and (iv) water; wherein the formulation maintains about 95% w/w or greater of the initial enalapril amount at the end of a storage period of at least 12 months at about 5±3° C. 2. The oral liquid formulation of claim 1 further comprising a sweetener. 3. The oral liquid formulation of claim 2, wherein the sweetener is sucralose. 4. The oral liquid formulation of claim 1 further comprising a flavoring agent. 5. The oral liquid formulation of claim 1, wherein the formulation does not contain mannitol. 6. The oral liquid formulation of claim 1, wherein the formulation does not contain silicon dioxide. 7. The oral liquid formulation of claim 1, wherein the buffer comprises about 0.8 to about 3.5 mg/ml citric acid. 8. The oral liquid formulation of claim 1, wherein the buffer comprises about 0.1 to about 0.8 mg/ml sodium citrate. 9. The oral liquid formulation of claim 1, wherein the pH of the oral liquid formulation is less than about 3.5. 10. The oral liquid formulation of claim 1, wherein the pH of the oral liquid formulation is between about 3 and about 3.5. 11. The oral liquid formulation of claim 1, wherein the pH of the oral liquid formulation is about 3.3. 12. The oral liquid formulation of claim 1, wherein the formulation maintains about 95% w/w or greater of the initial enalapril amount at the end of a storage period of at least 18 months at about 5±3° C. 13. An oral liquid formulation, consisting essentially of: (i) about 0.6 to about 1.2 mg/ml enalapril or a pharmaceutically acceptable salt or solvate thereof; (ii) a buffer comprising a mixture of citric acid and sodium citrate, wherein the buffer is present at a concentration between about 5 mM and about 20 mM in the oral liquid formulation; (iii) about 1 mg/ml sodium benzoate; (iv) water; and (v) optionally a sweetener, a flavoring agent, or both; wherein the formulation maintains about 95% w/w or greater of the initial enalapril amount at the end of a storage period of at least 12 months at about 5±3° C. 14. An oral liquid formulation, comprising: (i) about 0.6 to about 1.2 mg/ml enalapril or a pharmaceutically acceptable salt or solvate thereof; (ii) a buffer comprising a mixture of citric acid and sodium citrate, wherein the buffer is present at a concentration between about 5 mM and about 20 mM in the oral liquid formulation; (iii) about 1 mg/ml of a preservative, wherein the preservative is a paraben or a mixture of parabens; and (iv) water; wherein the formulation maintains about 95% w/w or greater of the initial enalapril amount at the end of a storage period of at least 12 months at about 5±3° C. 15. The oral liquid formulation of claim 14 further comprising a sweetener. 16. The oral liquid formulation of claim 15, wherein the sweetener is sucralose. 17. The oral liquid formulation of claim 14 further comprising a flavoring agent. 18. The oral liquid formulation of claim 14, wherein the formulation does not contain mannitol. 19. The oral liquid formulation of claim 14, wherein the formulation does not contain silicon dioxide. 20. The oral liquid formulation of claim 14, wherein the pH of the oral liquid formulation is less than about 3.5. 21. The oral liquid formulation of claim 14, wherein the pH of the oral liquid formulation is between about 3 and about 3.5. 22. The oral liquid formulation of claim 14, wherein the pH of the oral liquid formulation is about 3.3. 23. The oral liquid formulation of claim 14, wherein the formulation maintains about 95% w/w or greater of the initial enalapril amount at the end of a storage period of at least 18 months at about 5±3° C. 24. The oral liquid formulation of claim 1, wherein the enalapril or a pharmaceutically acceptable salt or solvate thereof is enalapril maleate, and wherein the enalapril maleate is present in the oral liquid formulation at about 1.0 mg/ml. 25. The oral liquid formulation of claim 1, wherein the buffer is present at a concentration between about 10 mM and about 20 mM in the oral liquid formulation. 26. The oral liquid formulation of claim 1, wherein the buffer is present at a concentration of about 10 mM in the oral liquid formulation. 27. The oral liquid formulation of claim 14, wherein the enalapril or a pharmaceutically acceptable salt or solvate thereof is enalapril maleate, and wherein the enalapril maleate is present in the oral liquid formulation at about 1.0 mg/ml. 28. The oral liquid formulation of claim 14, wherein the buffer is present at a concentration between about 10 mM and about 20 mM in the oral liquid formulation.