Epinephrine spray formulations
Inventors
Hartman, Steven • LOBEL, Michelle • Robben, Matthew P. • Dretchen, Kenneth L. • MESA, Michael
Assignees
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Publication Number
US-11000489-B2
Publication Date
2021-05-11
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 a pharmaceutical nasal spray formulation that is an aqueous solution suitable for administration as a spray into a nostril of a human subject. The formulation comprises epinephrine, or a pharmaceutically acceptable salt thereof, in water together with diethylene glycol monoethyl ether, hypromellose, sodium metabisulfite, chlorobutanol, citric acid monohydrate, and sodium chloride at defined concentrations.
A key aspect of the formulation is the limitation on impurities during storage. The formulation comprises no more than 2% total impurities after storage for a period of one month at a temperature of about 40 C.
The disclosure further describes formulation parameters including a pH range from about 4.0 to about 6.5, and spray/product characteristics based on droplet/plume geometry and droplet size distribution metrics. It also describes pharmacokinetic outcomes characterized by Cmax, Tmax, and AUC, together with early plasma epinephrine exposure and stability/impurity profiles over time and temperature.
Claims Coverage
The independent claims cover an aqueous pharmaceutical nasal spray formulation suitable for spraying into a human nostril, with defined epinephrine amounts, defined excipient concentrations, and a storage impurity limit. Across the independent claims, there are three epinephrine concentrations and a shared set of formulation and stability features.
Aqueous nasal spray epinephrine formulation with specified excipient concentrations
A pharmaceutical nasal spray formulation comprising epinephrine, or a pharmaceutically acceptable salt thereof, in water, together with diethylene glycol monoethyl ether, hypromellose, sodium metabisulfite, chlorobutanol, citric acid monohydrate, and sodium chloride at defined w/w amounts, wherein the formulation is an aqueous solution suitable for administration as a spray into a nostril of a human subject.
Impurity-limited nasal spray after storage at about 40 C
The formulation comprises no more than 2% total impurities after storage for a period of one month at a temperature of about 40 C.
Epinephrine nasal spray formulation with about 2% epinephrine (w/w)
The pharmaceutical nasal spray formulation has about 2% (w/w) of epinephrine, or a pharmaceutically acceptable salt thereof, in water, with the additional specified excipients at the stated w/w amounts and the aqueous-spray suitability for administration into a nostril of a human subject.
Epinephrine nasal spray formulation with about 6.5% epinephrine (w/w)
The pharmaceutical nasal spray formulation has about 6.5% (w/w) of epinephrine, or a pharmaceutically acceptable salt thereof, in water, with the additional specified excipients at the stated w/w amounts and the aqueous-spray suitability for administration into a nostril of a human subject.
Epinephrine nasal spray formulation with about 6% epinephrine (w/w)
The pharmaceutical nasal spray formulation has about 6% (w/w) of epinephrine, or a pharmaceutically acceptable salt thereof, in water, with the additional specified excipients at the stated w/w amounts and the aqueous-spray suitability for administration into a nostril of a human subject.
Across the independent claims, coverage is directed to an aqueous epinephrine nasal spray comprising defined excipients and concentrations, suitable for spraying into a human nostril, and having a stability and quality limitation of no more than 2% total impurities after one month at about 40 C.
Stated Advantages
Nasal delivery is described as providing higher plasma epinephrine exposure than injection.
Nasal delivery is described as rapidly achieving therapeutic plasma levels.
Provides formulation storage stability with no more than 2% total impurities after one month at about 40 C.
Provides a pharmaceutical nasal spray formulation suitable for administration as a spray into a nostril of a human subject.
Documented Applications
Treatment methods for anaphylaxis and anaphylactic shock using nasal spray delivery.
Treatment of respiratory depression using nasal spray delivery.
Intranasal administration of epinephrine for reaching therapeutic plasma concentrations and addressing effects related to nasal congestion.
Nasal administration as a spray into a nostril of a human subject.
Treating anaphylaxis and anaphylactic shock, including severe allergic reaction and related symptoms such as bronchial constriction, using an intranasal epinephrine spray formulation.
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