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 . An apparatus for delivery of a spray dried powder pharmaceutical composition, the apparatus comprising:
a reservoir containing a dose of the spray dried powder pharmaceutical composition, wherein the spray dried powder pharmaceutical composition comprises epinephrine or a pharmaceutically acceptable salt thereof and a carrier, wherein the spray dried powder pharmaceutical composition has a bulk particle size distribution characterized by a Dv50 of between about 5 microns and about 30 microns;
an air delivery assembly configured to be placed in fluid communication with the reservoir; and
a delivery head operatively coupled to the reservoir, wherein the delivery head defines a delivery aperture;
wherein upon actuation of the apparatus, the air delivery assembly is configured to produce an airflow through the reservoir to deliver a mixture of the airflow and the dose of the spray dried powder pharmaceutical composition via the delivery aperture, wherein the mixture has an emitted particle size distribution characterized by a Dv50 of between about 15 microns and about 200 microns and that is greater than the Dv50 of the bulk particle size distribution.
2 . The apparatus 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.
3 . The apparatus of claim 1 , wherein the bulk particle size distribution is characterized by a Dv90 of between about 13 microns and about 50 microns, wherein the emitted particle size distribution is characterized by a Dv90 of between about 475 microns and about 625 microns.
4 . The apparatus of claim 1 , wherein the Dv50 of the bulk particle size distribution is between about 5 microns and about 18 microns and wherein the Dv50 of the emitted particle size distribution is between about 20 microns and about 185 microns.
5 . The apparatus of claim 1 , wherein the spray dried powder pharmaceutical composition has a moisture content of between about 3% and about 6%.
6 . The apparatus of claim 1 , wherein the dose contains between about 3.5 mg and about 5.5 mg of the epinephrine or the pharmaceutically acceptable salt.
7 . The apparatus of claim 1 , wherein the spray dried powder pharmaceutical composition further comprises a dispersing agent.
8 . The apparatus of claim 1 , wherein the air delivery assembly includes an air chamber and a piston configured to be moved within the air chamber to produce the airflow through the reservoir.
9 . The apparatus of claim 8 , wherein the apparatus is configured to be manually actuated by the piston moving within the air chamber.
10 . The apparatus of claim 1 , wherein the spray dried powder pharmaceutical composition does not include an alpha-adrenergic blocker.
11 . An apparatus for delivery of a spray dried powder pharmaceutical composition, the apparatus comprising:
a reservoir containing a dose of the spray dried powder pharmaceutical composition, wherein the spray dried powder pharmaceutical composition comprises epinephrine or a pharmaceutically acceptable salt thereof, wherein the spray dried powder pharmaceutical composition has a bulk particle size distribution characterized by a Dv50 of between about 5 microns and about 18 microns;
an air delivery assembly configured to be placed in fluid communication with the reservoir; and
a delivery head operatively coupled to the reservoir, the delivery head defining a delivery aperture;
wherein upon actuation of the apparatus, the air delivery assembly is configured to produce an airflow through the reservoir to deliver a mixture of the airflow and the dose of the spray dried powder pharmaceutical composition via the delivery aperture, wherein the mixture has an emitted particle size distribution characterized by a Dv50 of between about 20 microns and about 185 microns and that is greater than the Dv50 of the bulk particle size distribution.
12 . The apparatus of claim 11 , wherein the spray dried powder composition further includes a carrier.
13 . The apparatus of claim 12 , wherein the carrier is lactose monohydrate.
14 . The apparatus of claim 11 , wherein the spray dried powder pharmaceutical composition does not include an alpha-adrenergic blocker.
15 . The apparatus of claim 11 , 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.
16 . The apparatus of claim 11 , wherein the bulk particle size distribution is characterized by a Dv90 of between about 13 microns and about 50 microns, wherein the emitted particle size distribution is characterized by a Dv90 of between about 475 microns and about 625 microns.
17 . The apparatus of claim 11 , wherein the dose contains between about 3.5 mg and about 5.5 mg of the epinephrine or the pharmaceutically acceptable salt.
18 . A spray dried powder pharmaceutical composition comprising:
epinephrine or a pharmaceutically acceptable salt thereof; and
a carrier;
wherein a single dose of the spray dried powder pharmaceutical composition contains about 3.5 mg to about 5.5 mg of epinephrine or the pharmaceutically acceptable salt thereof;
wherein the spray dried 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 spray dried powder pharmaceutical composition is formulated such that intranasal delivery of the dose of the spray dried powder pharmaceutical composition through an apparatus comprising an air delivery assembly and a delivery aperture produces a spray having an emitted particle size distribution characterized by a Dv50 of between about 15 microns and about 200 microns and that is greater than the Dv50 of the bulk particle size distribution.
19 . The spray dried powder pharmaceutical composition of claim 18 , wherein the spray dried powder pharmaceutical composition does not include an alpha-adrenergic blocker.
20 . The spray dried powder pharmaceutical composition of claim 18 , wherein the carrier includes any of mannitol, a cyclodextrin, citric acid, lactose, or sodium carboxymethylcellulose.