Intranasal epinephrine formulations and methods for the treatment of disease
Inventors
Lowenthal, Richard • Maggio, Edward T. • Bell, Robert G. • Shah, Pratik
Assignees
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Publication Number
US-12324838-B2
Publication Date
2025-06-10
Expiration Date
Abstract
Drug products adapted for nasal delivery comprising formulations with epinephrine and devices comprising such formulations are provided. Methods of treating anaphylaxis with epinephrine products are also provided.
Core Innovation
The disclosure relates to intranasal epinephrine formulations and single-use, pre-primed nasal spray devices for delivering an adrenergic-receptor mediated therapy. It further relates to intranasal, needle-free epinephrine drug products and treatment methods for anaphylaxis and type-1 hypersensitivity reactions involving adrenergic receptors.
The formulations include epinephrine or a salt thereof in water together with an alkyl glycoside absorption enhancer, in particular dodecyl maltoside, with optional inclusion of tetradecyl maltoside, sucrose dodecanoate, benzalkonium chloride, EDTA or disodium EDTA, antioxidants, stabilizing components, and pH adjustment agents. The intranasal formulation is described as using transmucosal absorption enhancement associated with increased paracellular permeability and possible transcytosis, with a short-lived effect.
The nasal spray device context specifies a single reservoir, a pre-primed state, and delivery by one actuation into one nostril of a human. The device delivers about 100 µL of nasal spray pharmaceutical formulation per actuation, with formulation volume between about 100 µL and about 140 µL, and the formulation includes epinephrine within specified mg/mL ranges with final pH adjusted between about 2.0 and about 6.0 or between about 3.0 and about 5.0 depending on the claim set.
Claims Coverage
The partial content provides seven independent claims. Across the independent claims, the main inventive features are directed to single-use, pre-primed nasal spray device structures and specific compositions and quantitative constraints for intranasal epinephrine formulated with an alkyl glycoside and adjusted pH.
Single-use, pre-primed nasal spray device delivering about 100 µL with an alkyl glycoside epinephrine formulation
A single-use, pre-primed nasal spray device comprising a single reservoir containing a nasal spray pharmaceutical formulation with a volume between about 100 µL and about 140 µL, where the formulation consists of epinephrine or a salt thereof, water, an alkyl glycoside, one or more isotonicity agents, and optionally EDTA, benzalkonium chloride, antioxidants, and pH adjustment agents to adjust to a final pH between about 2.0 and about 6.0, wherein one actuation delivers about 100 µL into one nostril of a human.
Single-dose pre-primed nasal spray device with 1 mg epinephrine formulation at final pH about 3.0 to about 5.0
A single-use, pre-primed nasal spray device comprising a single reservoir containing a single-dose nasal spray pharmaceutical formulation, wherein one actuation emits about 100 µL and the emitted formulation consists of 1 mg of epinephrine, water, dodecyl maltoside, sodium chloride, benzalkonium chloride, disodium salt of EDTA, sodium metabisulfite, and hydrochloric acid, sodium hydroxide, or both to adjust the pH to a final pH between about 3.0 and about 5.0.
Single-dose pre-primed nasal spray device with 2 mg epinephrine formulation at final pH about 3.0 to about 5.0
A single-use, pre-primed nasal spray device comprising a single reservoir containing a single-dose nasal spray pharmaceutical formulation, wherein one actuation emits about 100 µL and the emitted formulation consists of 2 mg of epinephrine, water, dodecyl maltoside, sodium chloride, benzalkonium chloride, disodium salt of EDTA, sodium metabisulfite, and hydrochloric acid, sodium hydroxide, or both to adjust the pH to a final pH between about 3.0 and about 5.0.
Pre-primed nasal spray device with formulation of about 10 mg/mL or about 20 mg/mL epinephrine and delivery about 100 µL
A single-use, pre-primed nasal spray device comprising a single reservoir containing a nasal spray pharmaceutical formulation having a volume between about 100 µL and about 140 µL, where the formulation consists of about 10 mg/mL or 20 mg/mL of epinephrine, water, dodecyl maltoside, sodium chloride, EDTA or disodium salt, benzalkonium chloride, sodium metabisulfite, and hydrochloric acid, sodium hydroxide, or both to adjust to a final pH between about 3.0 and about 5.0, and wherein one actuation delivers about 100 µL into one nostril of a human.
Pre-primed nasal spray device with epinephrine 3–20 mg/mL, DDM, sodium chloride, EDTA, benzalkonium chloride, optional sodium metabisulfite, and final pH about 3.0 to about 5.0
A single-use, pre-primed nasal spray device comprising a single reservoir containing a nasal spray pharmaceutical formulation having a volume between about 100 µL and about 140 µL, where the formulation consists of epinephrine at one of about 3 mg/mL through about 20 mg/mL, water, between about 0.15% (w/v) and about 0.35% (w/v) of dodecyl maltoside, between about 0.2% (w/v) and about 1.2% (w/v) of sodium chloride, EDTA or disodium salt, between about 0.001% (w/v) and about 0.2% (w/v) of benzalkonium chloride, optionally sodium metabisulfite, and hydrochloric acid, sodium hydroxide, or both to adjust the pH to a final pH between about 3.0 and about 5.0, wherein one actuation delivers about 100 µL into one nostril of a human.
Across the independent claims, the core claim coverage centers on a single-use, pre-primed nasal spray device with a single reservoir that delivers about 100 µL into one nostril of a human, together with intranasal epinephrine formulations in water containing an alkyl glycoside, including dodecyl maltoside, with sodium chloride, EDTA or disodium EDTA, benzalkonium chloride, and optionally sodium metabisulfite, with final pH constrained to about 3.0 to about 5.0 in several claim sets or broader final pH between about 2.0 and about 6.0 in one claim set.
Stated Advantages
Need for rapid needle-free intranasal dosing for anaphylaxis and type-1 hypersensitivity reactions involving adrenergic receptors.
Intranasal pharmacokinetic performance targets intended to mimic IM injection relationships of AUC and Cmax and to achieve a Tmax consistent with rapid early absorption.
Documented Applications
Treatment of anaphylaxis and type-1 hypersensitivity reactions involving adrenergic receptors using intranasal, needle-free epinephrine drug products.
Use of the disclosed single-use, pre-primed nasal spray device for delivering a nasal spray pharmaceutical formulation into one nostril of a human upon one actuation.
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