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 a single dose of the dry powder pharmaceutical composition;
wherein the dry powder pharmaceutical composition comprises epinephrine or a pharmaceutically acceptable salt thereof and a carrier;
wherein the dry powder pharmaceutical composition has a bulk particle size distribution characterized by a Dv50 of between about 5 microns and about 30 microns; and
wherein the dry powder pharmaceutical composition has an emitted particle size distribution characterized by a Dv50 of between about 25 microns and about 200 microns.
2 . The method of claim 1 , further comprising intranasally administering the dry powder pharmaceutical composition with a drug delivery device, wherein the drug delivery device includes a reservoir, an air delivery assembly, and a delivery head defining a delivery aperture.
3 . The method of claim 1 , wherein the carrier is lactose monohydrate.
4 . The method of claim 1 , wherein the bulk particle size distribution is characterized by a Dv10 of between about 1.5 microns and about 5 microns, wherein the emitted particle size distribution is characterized by a Dv10 of between about 5 microns and about 10 microns and is greater than the Dv10 of the bulk particle size distribution.
5 . The method of claim 1 , wherein the dose contains between about 2.0 mg and about 5.5 mg of the epinephrine or the pharmaceutically acceptable salt.
6 . The method of claim 1 , wherein the dry powder pharmaceutical composition has a moisture content of between about 3% and about 6%.
7 . The method of claim 1 , wherein the dry powder pharmaceutical composition does not include an alpha-adrenergic blocker.
8 . A method for intranasal administration of a dry powder pharmaceutical composition comprising:
intranasally administering to a human a single dose of the dry powder pharmaceutical composition;
wherein the dry powder pharmaceutical composition comprises epinephrine or a pharmaceutically acceptable salt thereof; and
wherein the dry powder pharmaceutical composition has an emitted particle size distribution characterized by a Dv50 of between about 25 microns and about 200 microns and that is greater than the Dv50 of the bulk particle size distribution.
9 . The method of claim 8 , wherein dry powder pharmaceutical composition further includes a carrier.
10 . The method of claim 9 , wherein the carrier is lactose monohydrate.
11 . The of method claim 8 , wherein the dry powder pharmaceutical composition has a bulk particle size distribution characterized by a Dv50 of between about 5 microns and about 30 microns.
12 . The method of claim 8 , wherein the dose contains between about 2.0 mg and about 5.5 mg of the epinephrine or the pharmaceutically acceptable salt.
13 . The method of claim 8 , wherein the dry powder pharmaceutical composition has a moisture content of between about 3.5% and about 6%.
14 . The method of claim 8 , wherein the dry powder pharmaceutical composition does not include an alpha-adrenergic blocker.
15 . The method of claim 8 , wherein:
a percentage of a total mass of the administered dry powder pharmaceutical composition to a mass of the administered dry powder composition that is deposited on a turbinate region and an olfactory region is greater than about 65%; and
a percentage of the total mass of the administered dry powder pharmaceutical composition to a mass of the administered dry powder composition that is deposited downstream of a nasopharynx is less than about 5%.
16 . The method of claim 8 , wherein the percentage of the total mass of the administered dry powder pharmaceutical composition to the mass of the administered dry powder composition that is deposited on the turbinate region and the olfactory region is between about 74% and about 85%.
17 . A dry powder pharmaceutical composition comprising:
epinephrine or a pharmaceutically acceptable salt thereof;
wherein a single dose of the dry powder pharmaceutical composition contains about 2.0 mg to about 5.5 mg of epinephrine or the pharmaceutically acceptable salt thereof; and
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 and that is greater than the Dv50 of a bulk particle size distribution.
18 . The dry powder pharmaceutical composition of claim 17 , wherein the dry powder pharmaceutical composition has a bulk particle size distribution characterized by a Dv50 of between about 5 microns and about 30 microns.
19 . The dry powder pharmaceutical composition of claim 17 , wherein the dry powder pharmaceutical composition further includes a carrier.
20 . The dry powder pharmaceutical composition of claim 19 , wherein the carrier is lactose monohydrate.