Epinephrine spray formulations
Inventors
Hartman, Steven • LOBEL, Michelle • Robben, Matthew P. • Dretchen, Kenneth L. • MESA, Michael
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-11723884-B2
Publication Date
2023-08-15
Expiration Date
Abstract
Provided herein are epinephrine spray formulations and methods of administering the same. Also provided herein are methods of treating anaphylaxis by administering epinephrine spray formulations to subjects in need of such treatment. The spray formulations contain epinephrine or a pharmaceutically acceptable salt thereof, one or more of an antioxidant, an antimicrobial preservative, an isotonicity agent, an absorption enhancer, a viscosity modifier, and/or a buffering agent.
Core Innovation
The invention provides a method of administering a pharmaceutical solution by delivering a spray plume from a device adapted for nasal delivery into a nostril of a subject in need thereof. The delivered spray volume is from about 20 μL to about 250 μL. The pharmaceutical solution comprises water and epinephrine, or a pharmaceutically acceptable salt thereof, together with chlorobutanol hemihydrate, sodium bisulfite or sodium metabisulfite, hypromellose, citric acid or citric acid monohydrate, sodium chloride, and diethylene glycol monoethyl ether.
The formulation is defined by a weight ratio of epinephrine to chlorobutanol hemihydrate of about 12:1 to about 30:1. The disclosure further describes controlling spray plume physical characteristics, including quantitative particle size distribution properties such as span and Dmax measured at defined distances from the device. Additional constraints specify delivery timing and device configurations including pre-primed, one-handed actuation and bi-dose delivery from a single reservoir.
The invention is directed to intranasal epinephrine for therapeutic plasma concentration outcomes and improved pharmacokinetics, including Cmax, Tmax, AUC, and bioavailability. The solution and delivery are described in the context of treating anaphylaxis, anaphylactic shock, severe allergic reaction, and bronchial constriction. The disclosed intranasal spray approach is linked to spray and droplet characteristics and device delivery-time and drainage constraints.
Claims Coverage
The provided excerpt includes three independent claims. Across these independent claims, the core inventive subject matter is nasal administration of an epinephrine-containing pharmaceutical solution as a spray plume delivered from a device adapted for nasal delivery, with a defined delivered spray volume and a specified formulation and epinephrine-to-chlorobutanol hemihydrate weight ratio. Dependent claim refinements further constrain plume particle-size distribution and device and dosing configurations.
Nasal spray plume delivery from a nasal-adapted device
Delivering a spray of a pharmaceutical solution from a device adapted for nasal delivery into a nostril of a subject in need thereof in a manner that delivers the pharmaceutical solution in a spray plume.
Delivered spray volume constraint
Delivering a volume of from about 20 μL to about 250 μL of spray.
Defined epinephrine formulation with specified excipients
Providing a pharmaceutical solution comprising water and from about 1% to about 10% (w/w) of epinephrine, or a pharmaceutically acceptable salt thereof; chlorobutanol hemihydrate; sodium bisulfite or sodium metabisulfite; hypromellose; citric acid or citric acid monohydrate; sodium chloride; and diethylene glycol monoethyl ether.
Epinephrine to chlorobutanol hemihydrate weight ratio
Having a pharmaceutical solution weight ratio of epinephrine to chlorobutanol hemihydrate of about 12:1 to about 30:1.
Quantitative spray plume particle-size distribution and device-adapted operation
Configuring the method so that the spray plume has a particle size distribution with a span no greater than about 2.2 or about 2.0 when measured 1 to 10 cm from the device, and/or using a device that produces a spray plume having a Dmax of less than about 28 mm or less than about 26 mm measured 1 to 10 cm from the device.
Delivery timing constraint
Employing a method in which the delivery time of the pharmaceutical solution is less than about 25 seconds.
Pre-primed, one-handed actuatable device configuration
Using a pre-primed, one-hand actuatable device.
Bi-dose device delivering two sprays from a single reservoir
Using a bi-dose device configured to deliver two sprays of a pharmaceutical solution from a single reservoir.
Epinephrine amount per spray constraint
Providing that the spray contains about 1 mg to about 10 mg of epinephrine or a pharmaceutically acceptable salt thereof, with further narrowing to about 6 mg in a dependent refinement.
Across the independent claims, the core is nasal administration of an epinephrine-containing pharmaceutical solution as a spray plume delivered from a device adapted for nasal delivery, using a defined delivered spray volume and a defined solution composition with a specified epinephrine-to-chlorobutanol hemihydrate weight ratio. Dependent claim refinements further constrain spray plume particle size distribution, delivery time, and specific device and dosing configurations such as pre-primed one-handed actuation and bi-dose operation.
Stated Advantages
Improved pharmacokinetics, including effects on Cmax, Tmax, AUC, and bioavailability.
Therapeutic plasma concentration outcomes are targeted.
Intramuscular injection equivalence is addressed for the intranasal approach.
Documented Applications
Treating anaphylaxis and anaphylactic shock using intranasal epinephrine spray delivered into a nostril.
Treating severe allergic reaction due to exposure or suspected exposure to an allergen.
Treating bronchial constriction using intranasal epinephrine.
Interested in licensing this patent?