Epinephrine spray formulations
Inventors
Hartman, Steven • LOBEL, Michelle • Robben, Matthew P. • Dretchen, Kenneth L. • MESA, Michael
Assignees
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Publication Number
US-12245995-B2
Publication Date
2025-03-11
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 epinephrine pharmaceutical spray formulations configured for administration as a nasal spray into a nostril of a subject. The formulations comprise epinephrine, or a pharmaceutically acceptable salt thereof, in water, ethanol, propylene glycol, or a combination thereof, together with an antimicrobial preservative including chlorobutanol or chlorobutanol hemihydrate. The formulation is configured to yield a plasma concentration of at least 0.4 ng/ml within 1 minute of nasal administration.
The invention further specifies a weight ratio of the epinephrine or pharmaceutically acceptable salt thereof to the chlorobutanol or chlorobutanol hemihydrate of about 12:1 to about 30:1. Optional additional formulation components include one or more of an antioxidant, an isotonicity agent, an absorption enhancer, a viscosity modifier, and a buffering agent. Diethylene glycol monoethyl ether is described as an absorption enhancer.
Stable pharmaceutical spray formulations are described that remain stable for at least about one month at a temperature of at least about 20° C., with embodiments requiring stability for at least one month at at least about 40° C. The disclosure also includes stability concepts involving impurity limits after storage.
Claims Coverage
The independent claims define three inventive features. Each centers on an epinephrine-containing nasal spray formulation preserved with chlorobutanol or chlorobutanol hemihydrate, with optional excipient classes and a required epinephrine-to-chlorobutanol weight ratio of about 12:1 to about 30:1.
Nasal spray epinephrine formulation with rapid plasma concentration and chlorobutanol preservation system
A pharmaceutical spray formulation comprising from about 1% to about 25% (w/w) epinephrine or a pharmaceutically acceptable salt thereof in water, ethanol, propylene glycol, or combinations thereof; an antimicrobial preservative including chlorobutanol or chlorobutanol hemihydrate and one or more of an antioxidant, an isotonicity agent, an absorption enhancer, a viscosity modifier, or a buffering agent; configured for administration into a nostril of a subject as a nasal spray that yields a plasma concentration of at least 0.4 ng/ml within 1 minute; with an epinephrine-to-chlorobutanol weight ratio of about 12:1 to about 30:1.
Stable nasal spray epinephrine formulation
A stable pharmaceutical spray formulation comprising from about 1% to about 25% (w/w) epinephrine or a pharmaceutically acceptable salt thereof in water, ethanol, propylene glycol, or combinations thereof; an antimicrobial preservative including chlorobutanol or chlorobutanol hemihydrate and one or more of an antioxidant, an isotonicity agent, an absorption enhancer, a viscosity modifier, or a buffering agent; stable for at least about one month at a temperature of at least about 20° C.; with an epinephrine-to-chlorobutanol weight ratio of about 12:1 to about 30:1.
Absorption enhancer specified as diethylene glycol monoethyl ether in the epinephrine nasal spray formulation
A pharmaceutical spray formulation comprising from about 1% to about 25% (w/w) epinephrine or a pharmaceutically acceptable salt thereof in water, ethanol, propylene glycol, or combinations thereof; an antimicrobial preservative including chlorobutanol or chlorobutanol hemihydrate and one or more of an antioxidant, an isotonicity agent, an absorption enhancer, a viscosity modifier, or a buffering agent; wherein the absorption enhancer is diethylene glycol monoethyl ether; and wherein the formulation has an epinephrine-to-chlorobutanol weight ratio of about 12:1 to about 30:1.
Across the independent claims, the core claim coverage is for an epinephrine-containing nasal spray formulation preserved with chlorobutanol or chlorobutanol hemihydrate, optionally including additional excipient classes, and constrained by an epinephrine:chlorobutanol weight ratio of about 12:1 to about 30:1. One independent claim further requires a plasma concentration of at least 0.4 ng/ml within 1 minute after nostril administration, another requires stability for at least about one month at at least about 20° C., and a further independent claim specifies diethylene glycol monoethyl ether as the absorption enhancer.
Stated Advantages
Yields a plasma concentration of at least 0.4 ng/ml within 1 minute of nasal administration.
Provides a stable pharmaceutical spray formulation for at least about one month at temperatures of at least about 20° C.
Stability can be achieved for at least about one month at a temperature of at least about 40° C.
Documented Applications
Administration into a nostril of a subject as a nasal spray configured to yield rapid plasma concentration.
Therapeutic use in anaphylaxis or anaphylactic shock and severe allergic reaction, including bronchial constriction.
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