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

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.

What is claimed is: 
     
         1 . A method, comprising:
 providing a naloxone composition configured for use in a medicament delivery device, the naloxone composition including a tonicity-adjusting agent, the pH of the naloxone composition ranging from 3 to 5; and   assembling the medicament delivery device, the medicament delivery device including a housing, a medicament container disposed within the housing and defining an internal volume containing the naloxone composition, an elastomeric member that seals the naloxone composition within the medicament container, and a delivery member coupled to the medicament container, and the assembling including removably coupling a cover or case to the housing of the medicament delivery device.   
     
     
         2 . The method of  claim 1 , wherein:
 the medicament delivery device is an auto-injector; and   the delivery member is a needle, the needle being coupled to the medicament container via a coupling member, the needle being fluidically isolated from the internal volume when the coupling member and the medicament container are in a first configuration, the needle in fluid communication with the internal volume when the coupling member and the medicament container are in a second configuration.   
     
     
         3 . The method of  claim 1 , wherein:
 the medicament delivery device is an intranasal spray device; and   the delivery member is associated with an atomizer defining an orifice through which the naloxone composition is delivered, the atomizer being coupled to the medicament container via a coupling member, the coupling member including a needle, the coupling member and the medicament container being in a first configuration prior to the medicament delivery device being removed from the case, an end portion of the needle being disposed outside of the internal volume when the coupling member and the medicament container are in the first configuration, the end portion of the needle disposed within the internal volume when the coupling member and the medicament container are in a second configuration.   
     
     
         4 . The method of  claim 1 , further comprising:
 storing the medicament delivery device within the case for at least six months.   
     
     
         5 . The method of  claim 1 , further comprising:
 removing the cover or case from the housing of the medicament delivery device.   
     
     
         6 . The method of  claim 1 , wherein the tonicity-adjusting agent includes sodium chloride in an amount such that a concentration of sodium chloride is between 0.1 mg/mL and 20 mg/mL. 
     
     
         7 . The method of  claim 1 , wherein the medicament container is a prefilled syringe. 
     
     
         8 . The method of  claim 1 , wherein the elastomeric member includes a silicone-based material. 
     
     
         9 . The method 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. 
     
     
         10 . The method 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. 
     
     
         11 . The method 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.   
     
     
         12 . The method of  claim 1 , 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. 
     
     
         13 . The method of  claim 12 , wherein the concentration of the 4,5-epoxy-3,14-dihydroxy-17-(2-propenyl)morphinan-6-one is about 10 mg/mL. 
     
     
         14 . An apparatus, comprising:
 a housing;   a medicament container within the housing, the medicament container defining an internal volume containing a naloxone composition, the naloxone composition including a tonicity-adjusting agent and a pH adjusting agent, the pH of the naloxone composition ranging from 3 to 5;   a delivery member coupled to the medicament container via a coupling member, the delivery member being fluidically isolated from the internal volume when the coupling member and the medicament container assembly are in a first configuration, the delivery member in fluid communication with the internal volume when the coupling member and the medicament container assembly are in a second configuration; and   an actuator coupled to the housing, the actuator configured to cause a force to be exerted to (1) transition the coupling member and the medicament container assembly from the first configuration to the second configuration and (2) deliver a single dose of the naloxone composition from the internal volume via the delivery member.   
     
     
         15 . The apparatus of  claim 14 , wherein a longitudinal axis of the actuator is non-coaxial with a longitudinal axis of the delivery member. 
     
     
         16 . An apparatus, comprising:
 a housing;   a medicament container disposed within the housing, the medicament container containing a single dose of a naloxone composition; and   an electronic circuit system coupled to the housing, the electronic circuit system configured to produce an output when the electronic circuit system is actuated.   
     
     
         17 . The apparatus of  claim 16 , wherein the output of the electronic circuit system is an audio or visual output indicating an aspect of the naloxone composition. 
     
     
         18 . The apparatus of  claim 16 , wherein the output of the electronic circuit system includes an expiration date of the naloxone composition. 
     
     
         19 . The apparatus of  claim 16 , wherein the output of the electronic circuit system includes instructions for disposal of the apparatus. 
     
     
         20 . The apparatus of  claim 16 , wherein the output of the electronic circuit system includes instructions for post-administration procedures.