Dry powder formulations of epinephrine and associated methods
Inventors
Lyman, Scott • Bleske, Barry • Lanpher, Ted William
Assignees
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Publication Number
US-11872308-B2
Publication Date
2024-01-16
Expiration Date
Abstract
Provided herein are dry powder formulations comprising epinephrine alone or in combination with at least one enabling agent suitable for nasal application. Also provided are unit dose forms and devices comprising such formulations and methods of using such formulations for the treatment of various conditions including anaphylaxis, anaphylactoid reaction, respiratory conditions, hemodynamic collapse, and for administration during cardiopulmonary arrest and other life-threatening conditions.
Core Innovation
The invention provides an intranasal device that administers a pharmaceutical composition as a dry powder. The pharmaceutical composition includes epinephrine or a pharmaceutically acceptable salt thereof in a dose of about 0.01 mg to about 10 mg and includes a polysorbate in a specified w/v range together with a carrier, while not including an alpha-adrenergic blocker.
In the disclosed embodiments, polysorbate is used together with carrier excipients to optimize systemic nasal delivery of epinephrine using dry-powder intranasal formulations. The disclosure links the formulation design to nasal-delivery devices that include an intranasal administration pathway involving nasal passages and nasal mucosa, and describes intranasal device features including a nasal probe and an actuator.
The document also describes a kit for intranasal administration including at least one intranasal device enclosed in a pouch and/or a hard case. Packaging concepts include desiccant and tamper-related/authentication elements, and optional electronic indicators, sensors, and wireless communication for tracking expiration or use and providing alerts.
Claims Coverage
The partial content includes three independent claims centered on dry-powder or spray-dried powder epinephrine formulations combined with polysorbate and a carrier, delivered by an intranasal device with a nasal probe and an actuator, while excluding an alpha-adrenergic blocker.
Intranasal dry-powder epinephrine formulation with polysorbate and excluded alpha-adrenergic blocker
A dry powder comprising epinephrine or a pharmaceutically acceptable salt thereof providing a dose of about 0.01 mg to about 10 mg, a polysorbate at about 0.01% w/v to about 5% w/v, and a carrier, wherein the pharmaceutical composition does not include an alpha-adrenergic blocker.
Intranasal device with nasal probe and actuator for dry-powder delivery
An intranasal device including a reservoir and a means for discharging one or more doses, wherein the reservoir contains a quantity of the pharmaceutical composition, and wherein the intranasal device further includes a nasal probe and an actuator.
Intranasal kit enclosed in a pouch and/or hard case
A kit for intranasal administration including at least one intranasal device enclosed in a pouch and/or a hard case, where the intranasal device includes a reservoir and a means for discharging one or more doses, and where the intranasal device further includes a nasal probe and an actuator.
Spray-dried powder epinephrine formulation with polysorbate 80 and excluded alpha-adrenergic blocker
A spray-dried powder comprising epinephrine or a pharmaceutically acceptable salt thereof providing a dose of about 0.01 mg to about 10 mg, polysorbate 80 at about 0.01% w/v to about 2% w/v, and a carrier, wherein the pharmaceutical composition does not include an alpha-adrenergic blocker.
Across the independent claims, the core inventive coverage is the combination of intranasal delivery hardware with a dry-powder or spray-dried powder epinephrine formulation that includes polysorbate, including polysorbate 80 in one claim, and a carrier, while excluding an alpha-adrenergic blocker.
Stated Advantages
Improved shelf life and reduced heat degradation compared to aqueous/auto-injectors.
Needle-free portable nasal delivery using an intranasal device.
Reduced dose uncertainty.
Avoidance of alpha-adrenergic blocker class vasodilators.
Polysorbate-containing compositions produce increased epinephrine availability and AUC with observed changes in kinetics.
Polysorbate is used together with carrier excipients to optimize systemic nasal delivery of epinephrine using dry-powder intranasal formulations.
Rats are not ideal for intranasal epinephrine pharmacokinetic evaluation.
Documented Applications
Emergency indications including anaphylaxis and cardiac arrest (CPR).
Organophosphorus toxin exposure.
Cyanide or hydrogen sulfide exposure.
Intranasal administration of epinephrine or a pharmaceutically acceptable salt thereof.
Pharmacokinetic evaluations in Sprague Dawley rats and in Beagle dogs, including comparison with an intramuscular comparator.
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