Medicament delivery device for administration of opioid antagonists including formulations for naloxone

• US 10,322,239 B2
• Filed: 10/30/2017
• Issued: 06/18/2019
• Est. Priority Date: 01/26/2011
• Status: Active Grant

• Current Assignee: Kaleo, Inc.
• Original Assignee: Kaleo, Inc.
• Inventors: Edwards, Eric S., Edwards, Evan T., Licata, Mark J., Meyers, Paul F., Blondino, Frank E.
• Primary Examiner(s): Hayman, Imani N
• Application Number:
  US15/797,844
• Publication Number:
  US 20180126082A1
• Time in Patent Office: 596 Days
• CPC Class Codes: A61M 11/00 Sprayers or atomisers specially adapted for therapeutic purposes in general B05B; aerosol containers B65D83/14
• CPC Class Codes: A61M 11/007 Syringe-type or piston-type sprayers or atomisers
• CPC Class Codes: A61M 15/08 Inhaling devices inserted into the nose
• CPC Class Codes: A61M 2202/048 Anaesthetics see also A61M19/00
• CPC Class Codes: A61M 5/2033 Spring-loaded one-shot injectors with or without automatic needle insertion multishot dosing syringes A61M5/31525, needle insertion only A61M5/3287
• CPC Class Codes: A61M 5/2046 Media being expelled from injector by gas generation, e.g. explosive charge
• CPC Class Codes: A61M 5/3129 Syringe barrels A61M5/3205 and A61M5/50 take precedence
• CPC Class Codes: A61M 5/3204 Needle cap remover, i.e. devices to dislodge protection cover from needle or needle hub, e.g. deshielding devices
• CPC Class Codes: A61M 5/3232 Semi-automatic needle retraction, i.e. in which triggering of the needle retraction requires a deliberate action by the user, e.g. manual release of spring-biased retraction means

Abstract

Medicament delivery devices for administration of opioid antagonists are described herein. In some embodiments, an apparatus includes a housing, a medicament container disposed within the housing and an energy storage member disposed within the housing. The medicament container is filled with a naloxone composition that includes naloxone or salts thereof, a tonicity-adjusting agent, and a pH-adjusting agent, whereby the osmolality of the naloxone composition ranges from about 250-350 mOsm and the pH ranges from about 3-5. The energy storage member is configured to produce a force to deliver the naloxone composition.

Claims

1. A method, comprising:

removing a medicament delivery device from a case;

the medicament delivery device including a housing, a prefilled medicament container assembly disposed within the housing, a medicament delivery structure disposed within the housing, and a movable member configured to cause a force to be exerted on the prefilled medicament container assembly, the prefilled medicament container assembly including a container, a naloxone composition contained within the container, the naloxone composition including a tonicity-adjusting agent and a pH adjusting agent, the pH of the naloxone composition ranging from about 3 to about 5, and an elastomeric member disposed within the container to seal the naloxone composition within the container, the elastomeric member formulated to be compatible with the naloxone composition when in contact with the naloxone composition for a time period of at least one year;

an end portion of the medicament delivery structure being fluidically isolated from the naloxone composition when the prefilled medicament container assembly is in a first position within the housing;

placing a distal end portion of the medicament delivery device into a position relative to a target location of a patient; and

moving the movable member to transmit the force to be exerted on the prefilled medicament container assembly to move the prefilled medicament container assembly from the first position to a second position within the housing, bringing the end portion of the medicament delivery structure into fluid communication with the naloxone composition when the prefilled medicament container assembly is in the second position within the housing, and delivering the naloxone composition via the medicament delivery structure.

2. The method of claim 1, wherein the medicament delivery structure is a needle.

3. The method of claim 2, wherein the force is a single force exerted in one direction on the prefilled medicament container assembly to both (1) move the prefilled medicament container assembly from the first position to the second position, and (2) deliver the naloxone composition via the needle.

4. The method of claim 1, wherein the medicament delivery structure is associated with an atomizer defining an orifice through which the naloxone composition is delivered intranasally to the patient.

5. The method of claim 1, wherein the medicament delivery structure is an atomizer configured to produce a spray of the naloxone composition having a droplet size distribution in which approximately 85 percent of the droplets have a size of between approximately 10 microns and 150 microns.

6. The method of claim 1, wherein the medicament delivery structure defines a part of a flow path through which the naloxone composition is delivered, the flow path in fluid communication with an orifice through which the naloxone composition is delivered intranasally to the patient.

7. The method of claim 1, wherein at least a portion of the elastomeric member is coated with a silicone-based material.

8. A method, comprising:

placing a distal end of a medicament delivery device into a delivery position, the medicament delivery device including a housing, a prefilled medicament container assembly disposed within the housing, a medicament delivery structure disposed within the housing, and a movable member configured to cause a force to be exerted on the prefilled medicament container assembly, the prefilled medicament container assembly including a container, a naloxone composition contained within the container, the naloxone composition including a tonicity-adjusting agent and a pH adjusting agent, the pH of the naloxone composition ranging from about 3 to about 5, and an elastomeric member disposed within the container to seal the naloxone composition within the container, the elastomeric member including a polymer and a curing agent, the elastomeric member formulated to minimize at least one of leaching or outgassing of compositions therein such that the elastomeric member is compatible with the naloxone composition when in contact with the naloxone composition for a time period of at least one year, an end portion of the medicament delivery structure being fluidically isolated from the naloxone composition when the prefilled medicament container assembly is in a first position within the housing; and

actuating the medicament delivery device by moving the movable member to transmit the force to be exerted on the prefilled medicament container assembly to move the prefilled medicament container assembly from the first position to a second position within the housing, bringing the end portion of the medicament delivery structure into fluid communication with the naloxone composition when the prefilled medicament container assembly is in the second position within the housing, and delivering the naloxone composition via the medicament delivery, structure.

9. The method of claim 8, wherein the medicament delivery structure is a needle.

10. The method of claim 9, wherein the force is a single force exerted in one direction on the prefilled medicament container assembly to both (1) move the prefilled medicament container assembly from the first position to the second position, and (2) deliver the naloxone composition via the needle.

11. The method of claim 8, wherein the medicament delivery structure is associated with an atomizer defining an orifice through which the naloxone composition is delivered intranasally to a patient.

12. The method of claim 8, wherein the medicament delivery structure is an atomizer configured to produce a spray of the naloxone composition having a droplet size distribution in which approximately 85 percent of the droplets have a size of between approximately 10 microns and 150 microns.

13. The method of claim 8, wherein the medicament delivery structure defines a part of a flow path through which the naloxone composition is delivered, the flow path in fluid communication with an orifice through which the naloxone composition is delivered intranasally to a patient.

14. The method of claim 8, wherein at least a portion of the elastomeric member is coated with a silicone-based material.

15. An apparatus, comprising:

a housing;

a prefilled syringe assembly disposed within the housing, the prefilled syringe assembly including a container, an elastomeric member disposed within the container, and a needle staked to a distal end portion of the container, the container containing a dose of a naloxone composition that includes a tonicity-adjusting agent and a pH adjusting agent, the pH of the naloxone composition ranging from about 3 to about 5, the elastomeric member disposed within the container to seal the naloxone composition within the container, the elastomeric member formulated to be compatible with the naloxone composition when in contact with the naloxone composition for a time period of at least one year; and

a movable member coupled to the housing, the movable member configured to transmit a force to be exerted on the elastomeric member of the prefilled syringe assembly to deliver the naloxone composition via the needle.

16. The apparatus of claim 15, further comprising a cover to at least partially enclose the housing and the prefilled syringe assembly.

17. The apparatus of claim 16, wherein the housing defines an opening through which the naloxone composition within the container can be viewed, and the cover obstructs a view through the opening when the housing is within the cover.

18. The apparatus of claim 15, further comprising:

an energy storage member configured to move the movable member to transmit the force to be exerted on the elastomeric member.

19. The apparatus of claim 15, wherein the housing defines an internal volume within which a proximal end portion of the prefilled syringe assembly is disposed before and during delivery of the naloxone composition via the needle, a distal end of the needle extending beyond a distal surface of the housing before and during delivery of the naloxone composition via the needle, a proximal end of the housing including a first stop surface and a second stop surface, the first stop surface configured to limit distal movement of the movable member when the movable member moves from a first position to a second position within the housing, the second stop surface configured limit distal movement of the elastomeric member within the prefilled syringe assembly.

20. The apparatus of claim 15, wherein the elastomeric member includes a silicone-based material.

21. The apparatus of claim 15, wherein the elastomeric member is formulated to be compatible with the naloxone composition when in contact with the naloxone composition for a time period of at least two years.

22. The apparatus of claim 15, wherein the elastomeric member is formulated to include a polymer and a curing agent, the polymer including at least one of bromobutyl or chlorobutyl, the curing agent including at least one of sulfur or a metal oxide.

23. The apparatus of claim 15, wherein the naloxone composition includes 4,5-epoxy-3,14-dihydroxy-17-(2-propenyl)morphinan-6-one in a concentration of between about 0.01 mg/mL and about 60 mg/mL.

24. The apparatus of claim 23, wherein the concentration of the 4,5-epoxy-3,14-dihydroxy-17-(2-propenyl)morphinan-6-one is about 10 mg/mL.

25. The apparatus of claim 15, wherein the movable member is configured to transmit the force to be exerted on the elastomeric member to deliver a single dose of between 3 mg and 24 mg of the naloxone composition via the needle.

26. The apparatus of claim 15, wherein the movable member is configured to transmit the force to be exerted on the elastomeric member to deliver a single dose of between 4 mg and 18 mg of the naloxone composition via the needle.