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 method of administering a pharmaceutical solution, comprising delivering a spray of the pharmaceutical solution from a device into a nostril of a subject in need thereof in a manner that delivers the pharmaceutical solution in a round spray plume with an ovality ratio less than about 1.4 when measured at a distance of from about 1 to about 10 cm from the device, wherein:
(i) the device is adapted for nasal delivery;
(ii) a volume of from about 20 μL to about 250 μL of spray is delivered; and
(iii) the pharmaceutical solution comprises from about 0.5 mg to about 100 mg of epinephrine, or a pharmaceutically acceptable salt thereof, and the pharmaceutical solution further comprises from about 0.01% to about 0.1% (w/w) of sodium bisulfite or sodium metabisulfite, and about 1% (w/w) diethylene glycol monoethyl ether.
2. The method of claim 1 , wherein the spray plume has a particle size distribution with a span of no more than about 2.2 when measured at a distance of from about 1 to about 10 cm from the device.
3. The method of claim 1 , wherein the spray plume has a Dmax of less than about 28 mm when measured at a distance of from about 1 to about 10 cm from the device.
4. The method of claim 1 , wherein the device is a bi-dose device configured to deliver two sprays of the pharmaceutical solution.
5. The method of claim 1 , wherein the device has a single reservoir containing from about 125 μL to about 250 μL of the pharmaceutical solution.
6. The method of claim 1 , wherein the device comprises:
(i) a vial comprising an opening;
(ii) a cannula; and
(iii) a rubber stopper;
wherein the rubber stopper is configured to occlude the opening of the vial, and wherein the cannula is configured to pierce the stopper when the plunger applies sufficient force to the cannula.
7. The method of claim 1 , wherein the device is a pre-primed device that is configured to be actuatable with one hand.
8. The method of claim 1 , wherein a delivery time of the pharmaceutical solution is less than about 25 seconds.
9. The method of claim 1 , wherein the subject is suffering from a severe allergic reaction from exposure or suspected exposure to an allergen.
10. The method of claim 9 , wherein the allergen is food, medication, or an insect bite or sting.
11. The method of claim 9 , wherein the subject exhibits one or more symptoms chosen from: respiratory depression or distress, airway constriction, wheezing, tingling hands, feet, mouth, or scalp, shortness of breath, swelling or inflammation of the face, eyes, lips, tongue, or throat, hives, central nervous system depression, cardiovascular depression, altered level consciousness, mydriatic pupils, hypoxemia, hypotension, unresponsiveness to stimulus, unconsciousness, stopped breathing, erratic or stopped pulse, or vomiting.
12. The method of claim 1 , wherein the subject exhibits respiratory depression or distress, or cardiovascular depression.
13. The method of claim 12 , wherein the subject is free from respiratory depression or distress for at least about 1 hour following the delivery of the pharmaceutical solution into the nostril of the subject.
14. A method of administering a pharmaceutical solution, comprising delivering a spray of the pharmaceutical solution from a device into a nostril of a subject in need thereof in a manner that delivers the pharmaceutical solution in a spray plume with a particle size distribution having a span of no more than about 2.2 when measured at a distance of from about 1 to about 10 cm from the device, wherein:
the device is adapted for nasal delivery;
(ii) a volume of from about 20 μL to about 250 μL of spray is delivered; and
(iii) the pharmaceutical solution comprises from about 0.5 mg to about 100 mg of epinephrine, or a pharmaceutically acceptable salt thereof, and the pharmaceutical solution further comprises from about 0.01% to about 0.1% (w/w) of sodium bisulfite or sodium metabisulfite, and about 1% (w/w) diethylene glycol monoethyl ether.
15. The method of claim 14 , wherein the particle size distribution has a span of no more than about 2.0 when measured at a distance of from about 1 to about 10 cm from the device.
16. The method of claim 14 , wherein the device has a single reservoir containing from about 125 μL to about 250 μL of the pharmaceutical solution.
17. The method of claim 14 , wherein the device is a bi-dose device configured to deliver two sprays of the pharmaceutical solution from a single reservoir.
18. A method for administering a pharmaceutical solution, comprising delivering a spray of the pharmaceutical solution from a device into a nostril of a subject in need thereof in a manner that delivers the pharmaceutical solution in a spray plume with a Dmax of less than about 28 mm when measured at a distance of from about 1 to about 10 cm from the device, wherein:
(i) the device is adapted for nasal delivery;
(ii) a volume of from about 20 μL to about 250 μL of spray is delivered; and
(iii) the pharmaceutical solution comprises from about 0.5 mg to about 100 mg of epinephrine, or a pharmaceutically acceptable salt thereof, and the pharmaceutical solution further comprises from about 0.01% to about 0.1% (w/w) of sodium bisulfite or sodium metabisulfite, and about 1% (w/w) diethylene glycol monoethyl ether.
19. The method of claim 18 , wherein the device is a bi-dose device configured to deliver two sprays of the pharmaceutical solution.
20. The method of claim 18 , wherein the Dmax is less than about 26 mm when measured at a distance of from about 1 to about 10 cm from the device.