Epinephrine spray formulations
Inventors
Hartman, Steven • LOBEL, Michelle • ROBBEN, Matthew P • Dretchen, Kenneth L. • MESA, Michael
Assignees
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Publication Number
US-10688044-B2
Publication Date
2020-06-23
Expiration Date
Abstract
Provided herein are epinephrine spray formulations. Also provided herein are methods of treating anaphylaxis by administering epinephrine spray formulations to subjects in need of such treatment.
Core Innovation
The invention relates to intranasal administration of epinephrine using a device adapted for nasal delivery that delivers a spray of a pharmaceutical solution into a nostril of a subject in need thereof. The delivered spray plume is characterized by geometric and particle-size distribution parameters measured at a distance of from about 1 to about 10 cm from the device, including a round spray plume with an ovality ratio less than about 1.4, a span of no more than about 2.2, or a Dmax of less than about 28 mm.
The pharmaceutical solution comprises from about 0.5 mg to about 100 mg of epinephrine, or a pharmaceutically acceptable salt thereof, together with sodium bisulfite or sodium metabisulfite and about 1% (w/w) diethylene glycol monoethyl ether. The spray volume is from about 20 μL to about 250 μL, and the document also identifies dependent variants for plume metrics and delivery configurations such as a bi-dose device delivering two sprays.
The disclosed use context includes intranasal administration studies, comparative intranasal dosing versus intramuscular injection, congestion-related conditions, and spray/aerosol plume metrics. The document further describes evaluations intended to demonstrate that intranasal epinephrine delivery produces the defined plume shape and particle-size distribution while supporting measured systemic exposure and safety-relevant outcomes, including assessments in relation to the blood-brain barrier.
Claims Coverage
The consolidated independent claims set includes three inventive methods. Across the independent claims, the inventive features focus on nasal-adapted spray delivery of an epinephrine-containing pharmaceutical solution with specified spray-plume characterization metrics, spray volume, and formulation composition.
Round spray plume with ovality ratio below 1.4
Delivering a spray from a device adapted for nasal delivery into a subject’s nostril so that the pharmaceutical solution is delivered in a round spray plume with an ovality ratio less than about 1.4 when measured at a distance of from about 1 to about 10 cm from the device.
Spray-plume particle size span constraint
Delivering the pharmaceutical solution as a spray plume having a particle size distribution with a span of no more than about 2.2 when measured at a distance of from about 1 to about 10 cm from the device.
Spray-plume Dmax constraint
Delivering the pharmaceutical solution as a spray plume with a Dmax of less than about 28 mm when measured at a distance of from about 1 to about 10 cm from the device.
Epinephrine formulation with sodium bisulfite/metabisulfite and diethylene glycol monoethyl ether
Formulating the pharmaceutical solution to comprise from about 0.5 mg to about 100 mg of epinephrine, or a pharmaceutically acceptable salt thereof, and further comprise from about 0.01% to about 0.1% (w/w) of sodium bisulfite or sodium metabisulfite and about 1% (w/w) diethylene glycol monoethyl ether.
Nasal dose spray volume range
Delivering a volume of from about 20 μL to about 250 μL of spray.
Across the independent claims, the core coverage is a nasal-adapted epinephrine spray method that specifies the delivered plume as round with ovality less than about 1.4 and/or a bounded particle-size distribution with span no more than about 2.2 and/or a bounded Dmax of less than about 28 mm, while delivering 20–250 μL of spray of a formulation containing epinephrine plus sodium bisulfite or sodium metabisulfite and about 1% (w/w) diethylene glycol monoethyl ether.
Stated Advantages
The document describes evaluations intended to demonstrate that intranasal epinephrine delivery produces the defined plume shape and particle-size distribution while supporting measured systemic exposure and safety-relevant outcomes, including assessments in relation to the blood-brain barrier.
The text further documents pharmacokinetic and pharmacodynamic comparisons of intranasal dosing versus intramuscular injection.
The text also documents spray performance metrics and stability results.
Documented Applications
Intranasal administration studies.
Comparative intranasal dosing versus intramuscular injection.
Assessments addressing blood-brain barrier outcomes.
Studies addressing congestion-related conditions.
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