Intranasal naloxone compositions and methods of making and using same

Abstract

Disclosed herein are compositions containing an opioid antagonist such as naloxone and one or more pharmaceutically acceptable excipients. The compositions may be used for intranasal delivery of Naloxone for the treatment of, for example, opioid overdose in an individual in need thereof. Also disclosed are methods of making compositions containing Naloxone, and devices for nasal delivery of naloxone compositions.

1 . A nasal spray composition comprising:
 (i) about 15 mg/ml to about 50 mg/ml of naloxone hydrochloride;   (ii) about 2 mM to about 12 mM of disodium ethylenediaminetetraacetic acid;   (iii) sodium chloride;   (iv) an amount of hydrochloric acid sufficient to achieve a pH from about 3 to about 5.5; and   (v) an aqueous carrier.   
     
     
         2 . A nasal spray composition comprising:
 (i) about 5 mg/ml to about 50 mg/ml of naloxone hydrochloride or a dihydrate thereof;   (ii) about 2 mM to about 20 mM of disodium ethylenediaminetetraacetic acid;   (iii) sodium chloride;   (iv) an amount of hydrochloric acid sufficient to achieve a pH from about 3 to about 5.5; and   (v) an aqueous carrier.   
     
     
         3 . The nasal spray composition of  claim 2 , comprising from about 15 mg/l to about 50 mg/ml of the naloxone hydrochloride or the dihydrate thereof. 
     
     
         4 . The nasal spray composition of  claim 2 , comprising from about 15 mg/l to about 40 mg/ml of the naloxone hydrochloride or the dihydrate thereof. 
     
     
         5 . The nasal spray composition of  claim 2 , comprising from about 2 mM to about 15 mM of the disodium ethylenediaminetetraacetic acid. 
     
     
         6 . The nasal spray composition of  claim 2 , comprising from about 2 mM to about 12 mM of the disodium ethylenediaminetetraacetic acid. 
     
     
         7 . The nasal spray composition of  claim 2 , comprising naloxone hydrochloride. 
     
     
         8 . The nasal spray composition of  claim 2 , comprising naloxone hydrochloride dihydrate. 
     
     
         9 . The nasal spray composition of  claim 2  which provides a naloxone T max  from about 5 minutes to about 30 minutes. 
     
     
         10 . The nasal spray composition of  claim 2  which provides a naloxone C max  from about 1 ng/ml to about 4 ng/ml. 
     
     
         11 . The nasal spray composition of  claim 2  which provides a naloxone AUC 0-inf  from about 2.5 ng·hr/ml to about 4.5 ng·hr/ml. 
     
     
         12 . A method of treating an opioid overdose in an individual in need thereof, the method comprising nasally administering to the individual a therapeutically effective amount of the nasal spray composition of  claim 1  to treat the opioid overdose. 
     
     
         13 . A method of treating an opioid overdose in an individual in need thereof, the method comprising nasally administering to the individual a therapeutically effective amount of the nasal spray composition of  claim 2  to treat the opioid overdose. 
     
     
         14 . A nasal spray composition comprising:
 (i) about 5 mg/ml to about 50 mg/ml of naloxone hydrochloride or a dihydrate thereof:   (ii) about 2 mM to about 15 mM of disodium ethylenediaminetetraacetic acid;   (iii) sodium chloride; and   (iv) an aqueous carrier.   
     
     
         15 . The nasal spray composition of  claim 14 , comprising from about 15 mg/l to about 50 mg/ml of the naloxone hydrochloride or the dihydrate thereof. 
     
     
         16 . The nasal spray composition of  claim 14 , comprising from about 15 mg/l to about 40 mg/ml of the naloxone hydrochloride or the dihydrate thereof. 
     
     
         17 . The nasal spray composition of  claim 14 , comprising from about 2 mM to about 12 mM of the disodium ethylenediaminetetraacetic acid. 
     
     
         18 . The nasal spray composition of  claim 14 , comprising naloxone hydrochloride. 
     
     
         19 . The nasal spray composition of  claim 14  having a pH from about 3 to about 5.5. 
     
     
         20 . A method of treating an opioid overdose in an individual in need thereof, the method comprising nasally administering to the individual a therapeutically effective amount of the nasal spray composition of  claim 14  to treat the opioid overdose.