Granted Patent
B2
US 12,734,138 · App. 17/582,045 · Granted Sep 15, 2026
Epinephrine fine particles and methods for use thereof
Inventors:
Mutasem Rawas-Qalaji (Fort Lauderdale, FL); Ousama Rachid (Winnipeg, CA); Keith Simons (Winnipeg, CA); Estelle Simons (Winnipeg, CA)
Assignee:
Nova Southeastern University
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Abstract
Compositions include epinephrine fine particles, including epinephrine nanoparticles or nanocrystals and epinephrine microparticles or microcrystals, and methods for therapeutic use of the compositions for the treatment of conditions responsive to epinephrine such as a cardiac event or an allergic reaction, particularly anaphylaxis. The epinephrine fine particles can be incorporated into orally-disintegrating and fast-disintegrating tablet pharmaceutical formulations and can significantly increase the sublingual bioavailability of epinephrine, and thereby reduce the epinephrine dose required.
Claims (28)
1 . A method for increasing absorption of epinephrine in a subject having a condition responsive to treatment with epinephrine, the method comprising:
providing a pharmaceutical composition formulated for buccal or sublingual administration including epinephrine bitartrate fine particles ranging in size from about 2.5 μm to about 100 μm and at least one inactive and non-toxic substance, the epinephrine bitartrate fine particles formed by homogenizing raw epinephrine bitartrate particles; and
administering the pharmaceutical composition to the subject, thereby increasing the absorption of epinephrine in the subject having the condition responsive to treatment with epinephrine;
wherein the epinephrine bitartrate fine particles formed by homogenizing raw epinephrine bitartrate particles have a spherical shape, the spherical shape formed when raw epinephrine bitartrate particles having a rectangular shape undergo a morphological change during homogenization to form the epinephrine bitartrate fine particles of the pharmaceutical composition.
2 . The method according to claim 1 , wherein the at least one inactive and non-toxic substance in the pharmaceutical composition is at least one of a surfactant, a penetration enhancer, a mucoadhesive, a diluent, a filler, a binder, a lubricant, a disintegrant, a flow agent, a taste enhancer, and a sweetening agent and mouthfeel enhancer.
3 . The method according to claim 1 , wherein the condition responsive to treatment with epinephrine is a cardiac event, an allergic reaction, or a breathing difficulty.
4 . The method according to claim 3 , wherein the cardiac event is cardiac arrest, the allergic reaction is at least one of anaphylaxis, asthma, and bronchial asthma, and the breathing difficulty is associated with at least one of anaphylaxis, asthma, bronchial asthma, bronchitis, emphysema, and a respiratory infection.
5 . The method according to claim 1 , wherein the pharmaceutical composition comprises a pharmaceutically effective dose of less than 40 mg of the epinephrine bitartrate fine particles.
6 . The method according to claim 1 , wherein the epinephrine bitartrate fine particles have a polydispersity (pdi) index between about 0.16 and about 0.20.
7 . The method according to claim 1 , wherein the condition responsive to treatment with epinephrine is an allergic reaction and the allergic reaction is at least one of anaphylaxis, asthma, and bronchial asthma.
8 . The method according to claim 1 , wherein the pharmaceutical composition comprises a pharmaceutically effective dose of 20 mg of the epinephrine bitartrate fine particles and, upon administration to the subject, the pharmaceutically effective dose of 20 mg provides a higher AUC in the subject as compared to an AUC of a 40 mg dose of raw epinephrine bitartrate particles.
9 . A method for treating a condition responsive to treatment with epinephrine in a subject in need thereof, the method comprising:
providing the pharmaceutical composition according to the method of claim 1 ; and
administering the pharmaceutical composition to the subject, thereby increasing absorption of epinephrine in the subject and treating the condition responsive to treatment with epinephrine in the subject.
10 . A method for increasing plasma concentration of epinephrine in a subject having a condition responsive to treatment with epinephrine, the method comprising:
providing the pharmaceutical composition according to the method of claim 1 ; and
administering the pharmaceutical composition to the subject, thereby increasing absorption of epinephrine in the subject and increasing the plasma concentration of epinephrine in the subject.
11 . The method according to claim 10 , further comprising evaluating the plasma concentration of epinephrine obtained in the subject following administration of the pharmaceutical composition to the subject.
12 . The method according to claim 11 , wherein the plasma concentration obtained is in a range substantially equivalent to that provided by a 0.3 mg intramuscular injection of epinephrine.
13 . A method for increasing absorption of epinephrine in a subject having a condition responsive to treatment with epinephrine, the method comprising:
providing a pharmaceutical composition formulated for buccal or sublingual administration including epinephrine bitartrate fine particles ranging in size from about 2.5 μm to about 100 μm and at least one inactive and non-toxic substance, the epinephrine bitartrate fine particles consisting of epinephrine bitartrate fine particles formed by homogenizing raw epinephrine bitartrate particles; and
administering the pharmaceutical composition to the subject, thereby increasing the absorption of epinephrine in the subject having the condition responsive to epinephrine;
wherein the epinephrine bitartrate fine particles formed by homogenizing raw epinephrine bitartrate particles have a spherical shape, the spherical shape formed when raw epinephrine bitartrate particles having a rectangular shape undergo a morphological change during homogenization to form the epinephrine bitartrate fine particles of the pharmaceutical composition.
14 . The method according to claim 13 , wherein the at least one inactive and non-toxic substance in the pharmaceutical composition is at least one of a surfactant, a penetration enhancer, a mucoadhesive, a diluent, a filler, a binder, a lubricant, a disintegrant, a flow agent, a taste enhancer, and a sweetening agent and mouthfeel enhancer.
15 . The method according to claim 13 , wherein the pharmaceutical composition comprises a pharmaceutically effective dose of less than 40 mg of the epinephrine bitartrate fine particles.
16 . The method according to claim 13 , wherein the epinephrine bitartrate fine particles have a polydispersity (pdi) index between about 0.16 and about 0.20.
17 . The method according to claim 13 , wherein the condition responsive to treatment with epinephrine is an allergic reaction and the allergic reaction is at least one of anaphylaxis, asthma, and bronchial asthma.
18 . The method according to claim 13 , wherein the pharmaceutical composition comprises a pharmaceutically effective dose of 20 mg of the epinephrine bitartrate fine particles and, upon administration to the subject, the pharmaceutically effective dose of 20 mg provides a higher AUC in the subject as compared to an AUC of a 40 mg dose of raw epinephrine bitartrate particles.
Continuity (6)
Provisional Application
61804892
· Mar 25, 2013
Provisional Application
61804519
· Mar 22, 2013
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