Enalapril formulations
View Patent ↗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.
1. A stable 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 about 0.8 to about 3.5 mg/ml citric acid and about 0.1 to about 0.8 mg/ml sodium citrate;
(iii) about 0.7 to about 1.2 mg/ml sodium benzoate; and
(iv) water;
wherein the formulation is stable at about 5±3° C. for at least 12 months; and
wherein the stable oral liquid formulation has about 95% w/w or greater of the initial enalapril amount and about 5% w/w or less total impurity or related substances at the end of the given storage period.
2. The stable oral liquid formulation of claim 1 further comprising about 0.5 to about 0.9 mg/ml sucralose.
3. The stable oral liquid formulation of claim 1 further comprising a flavoring agent.
4. The stable oral liquid formulation of claim 1 , wherein the formulation does not contain mannitol.
5. The stable oral liquid formulation of claim 1 , wherein the formulation does not contain silicon dioxide.
6. The stable oral liquid formulation of claim 1 , wherein the pH of the stable oral liquid formulation is less than about 3.5.
7. The stable oral liquid formulation of claim 1 , wherein the pH of the stable oral liquid formulation is between about 3 and about 3.5.
8. The stable oral liquid formulation of claim 1 , wherein the pH of the stable oral liquid formulation is about 3.3.
9. The stable oral liquid formulation of claim 1 , wherein the formulation is stable at about 5±3° C. for at least 18 months.
10. The stable oral liquid formulation of claim 1 , wherein the formulation is stable at about 5±3° C. for at least 24 months.
11. A stable oral liquid formulation, comprising:
(i) about 10% to about 25% (w/w of solids) enalapril or a pharmaceutically acceptable salt or solvate thereof;
(ii) a buffer comprising about 17% to about 47% (w/w of solids) citric acid and about 1% to about 11% (w/w of solids) sodium citrate;
(iii) about 3% to about 25% (w/w of solids) sodium benzoate; and
(iv) water;
wherein the formulation is stable at about 5±3° C. for at least 12 months; and
wherein the stable oral liquid formulation has about 95% w/w or greater of the initial enalapril amount and about 5% w/w or less total impurity or related substances at the end of the given storage period.
12. The stable oral liquid formulation of claim 11 further comprising about 8% to about 18% (w/w of solids) sucralose.
13. The stable oral liquid formulation of claim 11 further comprising a flavoring agent.
14. The stable oral liquid formulation of claim 11 , wherein the formulation does not contain mannitol.
15. The stable oral liquid formulation of claim 11 , wherein the formulation does not contain silicon dioxide.
16. The stable oral liquid formulation of claim 11 , wherein the pH of the stable oral liquid formulation is less than about 3.5.
17. The stable oral liquid formulation of claim 11 , wherein the pH of the stable oral liquid formulation is between about 3 and about 3.5.
18. The stable oral liquid formulation of claim 11 , wherein the pH of the stable oral liquid formulation is about 3.3.
19. The stable oral liquid formulation of claim 11 , wherein the formulation is stable at about 5±3° C. for at least 18 months.
20. The stable oral liquid formulation of claim 11 , wherein the formulation is stable at about 5±3° C. for at least 24 months.