Epinephrine spray formulations
Provided herein are epinephrine spray formulations. Also provided herein are methods of treating anaphylaxis by administering epinephrine spray formulations to subjects in need of such treatment.
1. A pharmaceutical nasal spray formulation, comprising:
(a) from about 1% to about 10% (w/w) of epinephrine, or a pharmaceutically acceptable salt thereof, in water;
(b) chlorobutanol or chlorobutanol hemihydrate;
(c) sodium bisulfite or sodium metabisulfite;
(d) hypromellose;
(e) citric acid or citric acid monohydrate;
(f) sodium chloride; and
(g) diethylene glycol monoethyl ether,
wherein the pharmaceutical nasal spray formulation has a weight ratio of epinephrine to chlorobutanol or chlorobutanol hemihydrate of about 12:1 to about 30:1.
2. The pharmaceutical nasal spray formulation of claim 1 , comprising chlorobutanol hemihydrate.
3. The pharmaceutical nasal spray formulation of claim 1 , comprising from about 0.01% to about 0.1% (w/w) of sodium bisulfite or sodium metabisulfite.
4. The pharmaceutical nasal spray formulation of claim 1 , comprising from about 0.01% to about 0.2% (w/w) of hypromellose.
5. The pharmaceutical nasal spray formulation of claim 1 , comprising from about 0.1% to about 1% (w/w) of citric acid or citric acid monohydrate.
6. The pharmaceutical nasal spray formulation of claim 1 , comprising from about 0.1% to about 1% (w/w) of sodium chloride.
7. The pharmaceutical nasal spray formulation of claim 1 , comprising from about 0.1% to about 5% (w/w) of diethylene glycol monoethyl ether.
8. The pharmaceutical nasal spray formulation of claim 1 , comprising from about 4% to about 10% (w/w) of epinephrine, or a pharmaceutically acceptable salt thereof, in water.
9. The pharmaceutical nasal spray formulation of claim 1 , comprising about 2% (w/w) of epinephrine, or a pharmaceutically acceptable salt thereof, in water.
10. The pharmaceutical nasal spray formulation of claim 1 , comprising about 6.5% (w/w) of epinephrine, or a pharmaceutically acceptable salt thereof, in water.
11. The pharmaceutical nasal spray formulation of claim 1 , comprising about 6% (w/w) of epinephrine, or a pharmaceutically acceptable salt thereof, in water.
12. The pharmaceutical nasal spray formulation of claim 1 , wherein a pH of the pharmaceutical nasal spray formulation is from about 4.0 to about 6.5.
13. A pharmaceutical nasal spray formulation, comprising:
(a) from about 1% to about 10% (w/w) of epinephrine, or a pharmaceutically acceptable salt thereof, in water;
(b) from about 0.1 to about 1.0% (w/w) of chlorobutanol or chlorobutanol hemihydrate;
(c) sodium bisulfite or sodium metabisulfite;
(d) hypromellose;
(e) citric acid or citric acid monohydrate;
(f) sodium chloride; and
(g) diethylene glycol monoethyl ether,
wherein the pharmaceutical nasal spray formulation has a weight ratio of epinephrine to chlorobutanol or chlorobutanol hemihydrate of about 12:1 to about 30:1.
14. The pharmaceutical nasal spray formulation of claim 13 , comprising from about 0.1 to about 1.0% (w/w) of chlorobutanol hemihydrate.
15. The pharmaceutical nasal spray formulation of claim 13 , comprising from about 0.01% to about 0.1% (w/w) of sodium bisulfite or sodium metabisulfite.
16. The pharmaceutical nasal spray formulation of claim 13 , comprising from about 0.01% to about 0.2% (w/w) of hypromellose.
17. The pharmaceutical nasal spray formulation of claim 13 , comprising from about 0.1% to about 1% (w/w) of citric acid or citric acid monohydrate.
18. The pharmaceutical nasal spray formulation of claim 13 , comprising from about 0.1% to about 1% (w/w) of sodium chloride.
19. The pharmaceutical nasal spray formulation of claim 13 , comprising from about 0.1% to about 5% (w/w) of diethylene glycol monoethyl ether.
20. The pharmaceutical nasal spray formulation of claim 13 , comprising from about 4% to about 10% (w/w) of epinephrine, or a pharmaceutically acceptable salt thereof, in water.
21. The pharmaceutical nasal spray formulation of claim 13 , comprising about 2% (w/w) of epinephrine, or a pharmaceutically acceptable salt thereof, in water.
22. The pharmaceutical nasal spray formulation of claim 13 , comprising about 6.5% (w/w) of epinephrine, or a pharmaceutically acceptable salt thereof, in water.
23. The pharmaceutical nasal spray formulation of claim 13 , comprising about 6% (w/w) of epinephrine, or a pharmaceutically acceptable salt thereof, in water.
24. The pharmaceutical nasal spray formulation of claim 13 , wherein the pH of the formulation is from about 4.0 to about 6.5.
25. A pharmaceutical nasal spray formulation, comprising:
(a) from about 1% to about 10% (w/w) of epinephrine, or a pharmaceutically acceptable salt thereof, in water;
(b) from about 0.1 to about 1.0% (w/w) of chlorobutanol or chlorobutanol hemihydrate;
(c) from about 0.01% to about 0.1% (w/w) of sodium bisulfite or sodium metabisulfite;
(d) from about 0.01% to about 0.2% (w/w) of hypromellose;
(e) from about 0.1% to about 1% (w/w) of citric acid or citric acid monohydrate;
(f) from about 0.1% to about 1% (w/w) of sodium chloride; and
(g) from about 0.1% to about 5% (w/w) of diethylene glycol monoethyl ether,
wherein the pharmaceutical nasal spray formulation has a weight ratio of epinephrine to chlorobutanol or chlorobutanol hemihydrate of about 12:1 to about 30:1.
26. The pharmaceutical nasal spray formulation of claim 25 , comprising from about 4% to about 10% (w/w) of epinephrine, or a pharmaceutically acceptable salt thereof, in water.
27. The pharmaceutical nasal spray formulation of claim 25 , comprising about 2% (w/w) of epinephrine, or a pharmaceutically acceptable salt thereof, in water.
28. The pharmaceutical nasal spray formulation of claim 25 , comprising about 6.5% (w/w) of epinephrine, or a pharmaceutically acceptable salt thereof, in water.
29. The pharmaceutical nasal spray formulation of claim 25 , comprising about 6% (w/w) of epinephrine, or a pharmaceutically acceptable salt thereof, in water.
30. The pharmaceutical nasal spray formulation of claim 25 , wherein the pH of the formulation is from about 4.0 to about 6.5.