Epinephrine spray formulations
Inventors
Hartman, Steven • LOBEL, Michelle • Robben, Matthew P. • Dretchen, Kenneth L. • MESA, Michael
Assignees
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Publication Number
US-12295921-B2
Publication Date
2025-05-13
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 provides a nasal delivery device adapted for delivery of a pharmaceutical nasal spray formulation into a nostril of a human subject as one or two nasal sprays. The nasal delivery device comprises a vial containing from about 125 μL to about 250 μL of the pharmaceutical nasal spray formulation, a cannula, a rubber stopper configured to occlude an opening of the vial, and a plunger, wherein the cannula is configured to pierce the rubber stopper when the plunger applies sufficient force.
The pharmaceutical nasal spray formulation comprises epinephrine, or a pharmaceutically acceptable salt thereof, in water at from about 1% to about 10% (w/w). The formulation further includes sodium bisulfite or sodium metabisulfite, chlorobutanol or chlorobutanol hemihydrate, and one or more of an absorption enhancer, a viscosity modifier, a buffering agent, and an isotonicity agent. The weight ratio of epinephrine or salt to chlorobutanol or chlorobutanol hemihydrate is about 12:1 to about 30:1.
In particular embodiments, the formulation includes diethylene glycol monoethyl ether as an absorption enhancer, polyethylene glycol, methylcellulose, hypromellose, or any combination thereof as a viscosity modifier, and citric acid, citrate, citric acid monohydrate, sodium phosphate, or sodium citrate as a buffering agent. The formulation also includes sodium chloride and no more than about 4% total impurities after storage for a period of one month at about 40°C.
The invention addresses treatment of anaphylaxis, including anaphylactic shock and related symptoms, using epinephrine nasal delivery with specified excipient composition, formulation stability, and defined delivery behavior.
Claims Coverage
The document includes two independent claims. The inventive features are the nasal delivery device structure and delivery configuration, the epinephrine-containing pharmaceutical nasal spray formulation, the specified excipient classes and ingredients, the defined epinephrine-to-chlorobutanol weight ratio, and the impurity limitation after storage.
Nasal delivery device for one or two nasal sprays into a nostril
A nasal delivery device comprising a vial containing from about 125 μL to about 250 μL of a pharmaceutical nasal spray formulation, a cannula, a rubber stopper configured to occlude an opening of the vial, and a plunger, wherein the cannula is configured to pierce the rubber stopper when the plunger applies sufficient force, and wherein the device administers the formulation into a nostril of a human subject as one or two nasal sprays.
Epinephrine formulation with antioxidant and antimicrobial preservative and defined epinephrine-to-chlorobutanol ratio
A pharmaceutical nasal spray formulation comprising epinephrine, or a pharmaceutically acceptable salt thereof, in water at from about 1% to about 10% (w/w), sodium bisulfite or sodium metabisulfite at from about 0.01% to about 0.1% (w/w), chlorobutanol or chlorobutanol hemihydrate, and one or more of an absorption enhancer, a viscosity modifier, a buffering agent, and an isotonicity agent, with a weight ratio of epinephrine or salt to chlorobutanol or chlorobutanol hemihydrate of about 12:1 to about 30:1.
Specific excipient classes with impurity limitation after storage
A pharmaceutical nasal spray formulation comprising epinephrine in water at from about 1% to about 10% (w/w), diethylene glycol monoethyl ether as an absorption enhancer, polyethylene glycol, methylcellulose, hypromellose, or any combination thereof as a viscosity modifier, sodium bisulfite or sodium metabisulfite as an antioxidant, chlorobutanol or chlorobutanol hemihydrate as an antimicrobial preservative, citric acid, citrate, citric acid monohydrate, sodium phosphate, or sodium citrate as a buffering agent, and sodium chloride, wherein the formulation has no more than about 4% total impurities after storage for one month at about 40°C and a weight ratio of epinephrine or salt to chlorobutanol or chlorobutanol hemihydrate of about 12:1 to about 30:1.
The inventive core centers on a nasal delivery device with a vial/cannula/rubber stopper/plunger arrangement configured to deliver an epinephrine nasal spray into a human nostril as one or two nasal sprays, together with a formulation having sodium bisulfite or sodium metabisulfite, chlorobutanol or chlorobutanol hemihydrate, and a defined epinephrine-to-chlorobutanol weight ratio. One independent claim further requires specified excipient identities and a limit on total impurities after storage.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Treatment of anaphylaxis, including anaphylactic shock and related symptoms.
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