COMPOSITIONS, DEVICES, AND METHODS FOR INTRANASAL DELIVERY OF DRY POWDER EPINEPHRINE
Intranasal dry powder epinephrine compositions are described herein. The compositions include epinephrine or a pharmaceutically acceptable salt thereof, as well as a stabilizing agent and a carrier. The stabilizing agent is operable to include citric acid, or a pharmaceutically acceptable salt derived therefrom. Such intranasal compositions as described herein are useful in the treatment of health conditions which threaten the central nervous system (CNS) and impede the actions of alpha and beta-adrenergic receptors. Such health conditions include anaphylaxis, bronchospasms, respiratory impairment, organophosphate poisoning, and major adverse cardiac events (MACE).
1 . A method for intranasal administration of a dry powder pharmaceutical composition comprising:
intranasally administering to a human with anaphylaxis a single dose of a dry powder pharmaceutical composition comprising about 3.5 mg to about 5.5 mg of epinephrine or a pharmaceutically acceptable salt thereof; and
wherein the intranasal administration of the single dose produces plasma epinephrine concentrations in the human with a time to reach a maximum epinephrine plasma concentration (Tmax) between about 15 minutes and about 30 minutes.
2 . The method of claim 1 , wherein the dry powder pharmaceutical composition does not include an alpha-adrenergic blocker.
3 . The method of claim 1 , wherein a mean baseline-corrected epinephrine concentration present in the human is at least 100 pg/mL after about 5 minutes after delivery of the single dose.
4 . The method of claim 1 , wherein the intranasal administration of the single dose produces plasma epinephrine concentrations in the human with the Tmax between about 18 minutes and about 28 minutes.
5 . The method of claim 1 , wherein the dry powder pharmaceutical composition is formulated such that delivery of the dose of the dry powder pharmaceutical composition produces a spray having an emitted particle size distribution characterized by a Dv50 of between about 25 microns and about 200 microns.
6 . The method of claim 1 , wherein the dry powder pharmaceutical composition further comprises a carrier, wherein the carrier includes any of mannitol, a cyclodextrin, citric acid, lactose, or sodium carboxymethylcellulose.
7 . The method of claim 6 , wherein the carrier includes lactose monohydrate.
8 . The method of claim 1 , wherein the dry powder pharmaceutical composition has a moisture content of between about 3% and about 6%.
9 . A method for intranasal administration of a dry powder pharmaceutical composition comprising:
intranasally administering a single dose of a dry powder pharmaceutical composition comprising about 3.5 mg to about 5.5 mg of epinephrine or a pharmaceutically acceptable salt thereof, and a carrier; and
wherein the intranasal administration of the single dose produces plasma epinephrine concentrations in the human with a time to reach a maximum epinephrine plasma concentration (Tmax) between about 15 minutes and about 30 minutes.
10 . The method of claim 9 , wherein the dry powder pharmaceutical composition does not include an alpha-adrenergic blocker.
11 . The method of claim 9 , wherein a mean baseline-corrected epinephrine concentration present is at least 100 pg/mL after about 5 minutes after delivery of the single dose.
12 . The method of claim 9 , wherein the dry powder pharmaceutical composition is formulated such that delivery of the dose of the dry powder pharmaceutical composition produces a spray having an emitted particle size distribution characterized by a Dv50 of between about 25 microns and about 200 microns.
13 . The method of claim 9 , wherein the carrier includes any of mannitol, a cyclodextrin, citric acid, lactose, or sodium carboxymethylcellulose.
14 . The method of claim 9 , wherein the carrier includes lactose monohydrate.
15 . The method of claim 9 , wherein the intranasal administration of the single dose produces plasma epinephrine concentrations in the human with the Tmax between about 18 minutes and about 28 minutes.
16 . A dry powder pharmaceutical composition comprising:
epinephrine or a pharmaceutically acceptable salt thereof; and
a carrier;
wherein a single dose of the dry powder pharmaceutical composition contains about 3.5 mg to about 5.5 mg of epinephrine or the pharmaceutically acceptable salt thereof; and
wherein the single dose of the dry powder pharmaceutical composition produces plasma epinephrine concentrations in a human with a time to reach a maximum epinephrine plasma concentration (Tmax) between about 15 minutes and about 30 minutes.
17 . The dry powder pharmaceutical composition of claim 16 , wherein the dry powder pharmaceutical composition does not include an alpha-adrenergic blocker.
18 . The dry powder pharmaceutical composition of claim 16 , wherein a mean baseline-corrected epinephrine concentration present is at least 100 pg/mL after about 5 minutes after delivery of the single dose.
19 . The dry powder pharmaceutical composition of claim 16 , wherein the dry powder pharmaceutical composition is formulated such that delivery of the dose of the dry powder pharmaceutical composition produces a spray having an emitted particle size distribution characterized by a Dv50 of between about 25 microns and about 200 microns.
20 . The dry powder pharmaceutical composition of claim 16 , wherein the carrier includes any of mannitol, a cyclodextrin, citric acid, lactose, or sodium carboxymethylcellulose.