Treatment with powdered intranasal epinephrine
Disclosed is a pharmaceutical composition in dry powder form for intranasal administration, comprising an anti-anaphylactic adrenergic receptor agonist in the form of dry powder for intranasal administration, the composition comprising solid particles of the active agent in combination with at least one functional additive, and solid particles of an inert carrier.
1 . A pharmaceutical composition comprising as an active agent an anti-anaphylactic adrenergic receptor agonist in the form of dry powder for intranasal administration, said composition comprising a first type of solid essentially spherical particles of a homogenous combination of said active agent in combination with at least one functional additive, and a second type of solid particles comprising a pharmaceutically acceptable carrier, wherein at least about 90% of said first type particles are of a mean particle size of about 10-30 microns and less than about 10% of said first type particles are of a mean particle size equal to or below about 10 microns and said second type particles are of a mean particle size of about 50-200 microns.
2 . The pharmaceutical composition of claim 1 , wherein said active agent is epinephrine or a pharmaceutically acceptable bitartrate, hydrochloride or borate salt thereof.
3 . The pharmaceutical composition of claim 1 , wherein said functional additive is sodium di-hydrogen phosphate.
4 . The pharmaceutical composition of claim 1 , wherein said carrier is any one of lactose monohydrate, lactose, a lactose functional analogue, or any mixture of at least two thereof.
5 . The pharmaceutical composition of claim 1 , wherein the first type particles and said second type particle are present at a weight ratio ranging from 1:9 to 9:1.
6 . An epinephrine pharmaceutical composition in the form of dry powder for intranasal administration, comprising as active agent epinephrine bitartrate, said composition comprising a first type of solid spherical particles comprising epinephrine bitartrate in combination with sodium di-hydrogen phosphate, and a second type of irregular solid particles comprising lactose monohydrate as carrier, wherein said first type spherical particles have a narrow size distribution of 5-30 μm, and are dispersed between said irregular particles of lactose ranging between 40 μm to 240 μm, providing a metered therapeutically effective nominal dose of said epinephrine bitartrate.
7 . The epinephrine pharmaceutical composition of claim 6 , wherein the molar ratio between the epinephrine bitartrate to sodium dihydrogen phosphate is 0.9:1.
8 . The epinephrine pharmaceutical composition of claim 6 , wherein said therapeutically effective amount of epinephrine bitartrate is about 4.8 mg to 8 mg, equivalent to about 0.3 mg or 0.5 mg epinephrine administered intramuscularly (i.m.).
9 . A disposable unit dosage form for intranasal administration to a subject of an epinephrine pharmaceutical composition according to claim 6 , wherein said disposable unit dosage form is loaded with a predetermined single dose of the composition and provides the subject with a metered dose epinephrine bitartrate.
10 . A disposable unit dosage form for intranasal administration to a subject of an epinephrine pharmaceutical composition according to claim 8 , wherein said disposable unit dosage form is loaded with a predetermined single dose of the composition and provides the subject with a metered dose of about 4.8 mg to 8 mg epinephrine bitartrate being equivalent to about 0.3 mg or 0.5 mg epinephrine bitartrate administered intramuscularly (i.m.).
11 . A method of treating anaphylactic shock in a patient in need thereof, said method comprising administering to said patient a therapeutically effective amount of a composition as defined in claim 1 .
12 . A method of treating anaphylactic shock in a patient in need thereof, said method comprising administering to said patient a therapeutically effective amount of an epinephrine composition as defined claim 8 .
13 . An epinephrine pharmaceutical composition in the form of dry powder for intranasal administration, comprising as active agent epinephrine bitartrate, said composition comprising a first type of solid spherical particles comprising epinephrine bitartrate in combination with sodium di-hydrogen phosphate, and a second type of irregular solid particles comprising lactose monohydrate as carrier, wherein the size distribution of the first type of solid spherical particles as determined by Malvern Laser Diffraction instrument is D=21.4 μm, D (50)=82.0 μm and D (90)=133 μm, and wherein the amount of the obtained particles having the size less than 10 μm is about 3.7% v/v and of particles having the size of less than 5 μm is about 2.8% v/v, providing a metered therapeutically effective nominal dose of said epinephrine or pharmaceutically acceptable salt thereof.