Epinephrine spray formulations
The present invention is directed to epinephrine spray formulations. The present invention is further directed to methods of treating anaphylaxis by administering epinephrine spray formulations to subjects in need of such treatments.
1. An epinephrine spray solution consisting of:
from about 0.1% w/w to about 15% w/w epinephrine or a salt thereof;
from 0.9% to 80% w/w water; and
optionally, one or more excipients selected from the group consisting of acids selected from the group consisting of hydrochloric acid, malic acid, tartaric acid, citric acid, succinic acid and combinations thereof, stabilizers selected from the group consisting of butylated hydroxyanisole, butylated hydroxytoluene, ascorbic acid, methionine, sodium ascorbate, sodium thiosulfate, sodium bisulfite, sodium metabisulfite, ascorbyl palmitate, thioglycerol, alpha tocopherol, cysteine hydrochloride, benzalkonium chloride, citric acid, ethylenediaminetetraacetic acid, sodium citrate, propyl gallate, 8-hydroxyquinoline, boric acid, histidine and combinations thereof, solvents, antioxidants, preservatives, permeation enhancers, viscosity modifiers, sweeteners, sweetness enhancers, pH modifiers, isotonicity agents and flavoring agents, wherein w/w denotes weight by weight of the solution and wherein the solution has a pH from about 2 to about 7.
2. The solution of claim 1 , wherein the solvent is at a concentration from about 1% w/w to about 99% w/w and is selected from the group consisting of ethanol, glycerin, propylene glycol, polyethylene glycol 400 and a combination thereof.
3. The solution of claim 1 , wherein the acid is at a concentration from about 0.1% w/w to about 60% w/w.
4. The solution of claim 1 , wherein the solution does not contain sorbitol.
5. The solution of claim 2 , wherein the solvent comprises from about 2% w/w to about 60% w/w ethanol.
6. The solution of claim 1 , wherein the acid is diluted hydrochloric acid.
7. The solution of claim 1 , wherein the epinephrine salts are selected from the group consisting of citrate, hydrochloride, halide, sulfate, bitartrate, tartrate, phosphate, acetate, malate, maleate, succinate, ascorbate, carbonate, mesylate and lactate.
8. The solution of claim 1 , wherein the stabilizer is selected from the group consisting of butylated hydroxyanisole, butylated hydroxytoluene, ascorbic acid, methionine, sodium ascorbate, sodium thiosulfate, sodium bisulfite, sodium metabisulfite, ascorbyl palmitate, thioglycerol, alpha tocopherol, cysteine hydrochloride, benzalkonium chloride, citric acid, edetate disodium dihydrate, sodium citrate, propyl gallate, 8-hydroxyquinoline, boric acid, histidine and combinations thereof.
9. The solution of claim 8 , wherein the stabilizer comprises edetate disodium dihydrate at a concentration from about 0.005% w/w to about 0.5% w/w.
10. The solution of claim 8 , wherein the stabilizer comprises sodium bisulfate or sodium metabisulfite or a combination thereof at a concentration from about 0.005% w/w to about 5 w/w.
11. The solution of claim 8 , wherein the stabilizer or chelating agent comprises benzalkonium chloride at a concentration from about 0.005% to about 0.5 w/w.
12. A method of treating anaphylaxis comprising administering the solution of claim 1 to a subject in need thereof.
13. The method of claim 12 , wherein the subject is suffering from nasal congestion.
14. The method of claim 12 , wherein administration occurs via an intranasal route.
15. The method of claim 12 , wherein administration occurs via a multi-dose device that delivers more than one dose of the solution of claim 1 to the subject.
16. The method of claim 15 , wherein the multi-dose device is a bi-dose device that delivers two doses of the solution of claim 1 to the subject.