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

• US 9,814,838 B2
• Filed: 01/26/2015
• Issued: 11/14/2017
• 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:
  US14/605,512
• Publication Number:
  US 20150231336A1
• Time in Patent Office: 1,023 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. An apparatus, comprising:

a housing;

a prefilled medicament container assembly disposed within the housing, 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;

a needle disposed within the housing, an end portion of the needle being fluidically isolated from the naloxone composition when the prefilled medicament container assembly is in a first position within the housing, the end portion of the needle being in fluid communication with the naloxone composition when the prefilled medicament container assembly is in a second position within the housing; and

a movable member configured to cause a force to be exerted on the prefilled medicament container assembly to move the prefilled medicament container assembly from the first position to the second position, and to deliver the naloxone composition via the needle.

2. The apparatus of claim 1, 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.

3. The apparatus of claim 1, wherein the prefilled medicament container assembly includes a single dose of the naloxone composition having an amount of about 1 mg.

4. The apparatus of claim 1, wherein:

the movable member includes a shoulder configured to contact an engagement portion, the shoulder configured to deform the engagement portion in response to the force; and

the elastomeric member is configured to move within the container in response to the force after the engagement portion is deformed.

5. The apparatus of claim 1, 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.

6. The apparatus of claim 1, 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.

7. The apparatus of claim 1, 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, the elastomeric member is 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 two years.

8. The apparatus of claim 1, wherein at least a portion of the elastomeric member includes a silicone-based material, the elastomeric member is 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 two years.

9. The apparatus of claim 1, wherein at least a portion of the elastomeric member is coated with polydimethylsiloxane in an amount of between approximately 0.02 mg/cm² and approximately 0.80 mg/cm².

10. The apparatus of claim 1, wherein:

the pH of the naloxone composition ranges from about 3.2-3.6;

the tonicity-adjusting agent includes at least one of dextrose, glycerin, mannitol, potassium chloride or sodium chloride; and

the elastomeric member includes a polymer and a curing agent, 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.

11. The apparatus of claim 1, wherein the naloxone composition includes at least one of a chelating agent or an antioxidant.

12. The apparatus of claim 1, further comprising:

an energy storage member disposed within the housing, the energy storage member configured to produce the force.

13. The apparatus of claim 1, wherein the movable member surrounds at least a portion of the prefilled medicament container assembly, the movable member configured to move in a first direction relative to the housing from an initial position to an actuated position to cause the force to be exerted on the prefilled medicament container assembly, the movable member includes a protrusion configured to engage a portion of the housing when the movable member is in the actuated position to limit movement of the movable member in a second direction opposite the first direction.

14. The apparatus of claim 1, wherein the housing defines a status window, a portion of the prefilled medicament container assembly being obstructed from view through the status window when the prefilled medicament container assembly is in the first position, the portion of the prefilled medicament container assembly being viewable through the status window when the prefilled medicament container assembly is in the second position.

15. An apparatus, comprising:

a housing;

a prefilled medicament container assembly disposed within the housing, 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;

a delivery member, the delivery member being fluidically isolated from the naloxone composition when the prefilled medicament container assembly is in a first position within the housing, the delivery member being in fluid communication with the naloxone composition when the prefilled medicament container assembly is in a second position within the housing; and

an actuator configured to cause a force to be exerted on the prefilled medicament container assembly to move the prefilled medicament container assembly from the first position to the second position, and to move the elastomeric member within the container to deliver the naloxone composition via the delivery member.

16. The apparatus of claim 15, wherein the actuator surrounds at least a portion of the prefilled medicament container assembly, the actuator configured to move in a first direction relative to the housing from an initial position to an actuated position to cause the force to be exerted on the prefilled medicament container assembly, the actuator includes a protrusion configured to engage a portion of the housing when the actuator is in the actuated position to limit movement of the actuator in a second direction opposite the first direction.

17. The apparatus of claim 15, wherein:

the actuator surrounds at least a portion of the prefilled medicament container assembly, the actuator includes a shoulder configured to contact an engagement portion, the shoulder configured to deform the engagement portion in response to the force; and

the elastomeric member is configured to move within the container in response to the force after the engagement portion is deformed.

18. The apparatus of claim 15, wherein the delivery member includes a needle.

19. The apparatus of claim 15, wherein the delivery member is configured to atomize the naloxone composition.

20. The apparatus of claim 15, wherein the delivery member is configured to produce an atomized spray of the naloxone composition, the atomized spray having a droplet size distribution wherein approximately 85 percent of droplets have a size of between approximately 10 microns and 150 microns.

21. The apparatus of claim 15, wherein:

the naloxone composition includes at least one of a chelating agent or an antioxidant; and

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 polymer includes at least one of bromobutyl or chlorobutyl, and the curing agent includes at least one of sulfur or a metal oxide.

23. The apparatus of claim 15, wherein at least a portion of the elastomeric member includes a silicone-based material.

24. The apparatus of claim 15, further comprising:

an energy storage member disposed within the housing, the energy storage member configured to produce the force.

25. The apparatus of claim 15, wherein the force is a first force, the apparatus further comprising:

a retraction spring having a portion disposed within the actuator, the retraction spring configured to exert a retraction force.

26. The apparatus of claim wherein 15, the housing defines a status window, a portion of the prefilled medicament container assembly being viewable through the status window.

27. An apparatus, comprising:

a housing;

a prefilled medicament container assembly disposed within the housing, the prefilled medicament container assembly including;

a container;

a naloxone composition contained within the container, the naloxone composition including at least one of a chelating agent or an antioxidant, 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 be compatible with the naloxone composition when in contact with the naloxone composition for a time period of at least one year;

a delivery member, the delivery member being fluidically isolated from the naloxone composition when the prefilled medicament container assembly is in a first position within the housing, the delivery member being in fluid communication with the naloxone composition when the prefilled medicament container assembly is in a second position within the housing; and

a movable member configured to matingly engage the prefilled medicament container assembly, the movable member including a shoulder configured to contact an engagement portion, the shoulder configured to deform the engagement portion, when the movable member is actuated, the actuator causing a force to be exerted 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) move, after the engagement portion is deformed, the elastomeric member within the container to deliver the naloxone composition via the delivery member.

28. The apparatus of claim 27, wherein the prefilled medicament container assembly includes a single dose of the naloxone composition having an amount of about 1 mg.

29. The apparatus of claim 27, 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.

30. The apparatus of claim 27, wherein the polymer includes at least one of bromobutyl or chlorobutyl, the curing agent includes at least one of sulfur or a metal oxide, the elastomeric member is 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 two years.

31. The apparatus of claim 27, wherein at least a portion of the elastomeric member includes a silicone-based material, the elastomeric member is 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 two years.

32. The apparatus of claim 27, further comprising:

an energy storage member disposed within the housing, the energy storage member configured to produce the force.

33. The apparatus of claim 27, wherein the force is a first force, the apparatus further comprising:

a retraction spring having a portion disposed within the actuator, the retraction spring configured to exert a retraction force.

34. The apparatus of claim 27, wherein the housing defines a status window, a portion of the prefilled medicament container assembly being viewable through the status window.