Intranasal Pharmaceutical Dosage Forms Comprising Naloxone

Abstract

The present invention relates to an intranasal pharmaceutical dosage form comprising a dosing unit comprising naloxone or a pharmaceutically acceptable salt thereof in an amount of equivalent to ≧0.5 mg naloxone HCl dissolved in an application fluid of a volume of ≦250 μl. Furthermore, the present invention relates to such an intranasal pharmaceutical dosage form for use in the treatment of opioid overdosing and/or at least one symptom thereof.

What is claimed is: 
     
         1 . An intranasal pharmaceutical dosage form, comprising a dosing unit comprising naloxone or a pharmaceutically acceptable salt thereof in an amount of equivalent to between about 0.65 mg naloxone HCl and about 0.8 mg naloxone HCl or between about 1.3 mg naloxone HCl and about 1.6 mg naloxone HCl dissolved in an application fluid having a volume less than or equal to about 250 μl. 
     
     
         2 . The intranasal pharmaceutical dosage form of  claim 1 , wherein the application fluid has a volume less than or equal to about 200 μl. 
     
     
         3 . The dosage form according to  claim 1 , wherein said dosing unit comprises naloxone or a pharmaceutically acceptable salt thereof in an amount equivalent to between about 0.65 mg naloxone HCl and about 0.8 mg naloxone HCl. 
     
     
         4 . The dosage form according to  claim 1 , wherein said dosing unit comprises naloxone or a pharmaceutically acceptable salt thereof in an amount equivalent to between about 1.3 mg naloxone HCl and about 1.6 mg naloxone HCl. 
     
     
         5 . The dosage form according to  claim 1 , wherein the volume of the application fluid ranges from about 200 μl to about 35 μl; from about 200 μl to about 50 μl; or from about 200 μl to about 100 μl. 
     
     
         6 . The dosage form according to  claim 1 , wherein the application fluid is water or an aqueous saline solution. 
     
     
         7 . The dosage form according to  claim 1 , wherein the application fluid is an aqueous saline solution. 
     
     
         8 . The dosage form according to  claim 7 , wherein the aqueous saline solution is a 0.9% (weight/volume) saline solution. 
     
     
         9 . The dosage form according to  claim 1 , wherein the dosage form is a nasal spray, a nasal mucoadhesive dosage form or a Mucosal Atomizer Device. 
     
     
         10 . A method of treating an opioid overdose or at least one symptom thereof, comprising intranasally administering a pharmaceutical dosage form comprising a total amount of naloxone or a pharmaceutically acceptable salt thereof dissolved in an application fluid, wherein the total amount of naloxone administered is equivalent to between about 1.3 mg naloxone HCl and about 1.6 mg naloxone HCl, wherein said total amount is provided by administration to one nostril or wherein said total amount is provided by administration to two nostrils, and wherein the volume of the application fluid per nostril is less than or equal to about 250 μl. 
     
     
         11 . The method of  claim 10 , wherein the volume of the application fluid per nostril is less than or equal to about 200 μl. 
     
     
         12 . The method according to  claim 10 , wherein the amount of naloxone or a pharmaceutically acceptable salt thereof is equivalent to an amount of naloxone HCl selected from the group consisting of about 1.3 mg naloxone HCl; about 1.4 mg naloxone HCl; about 1.5 mg naloxone HCl; and about 1.6 mg naloxone HCl. 
     
     
         13 . The method according to  claim 10 , wherein the volume of the application fluid per nostril ranges from about 200 μl to about 35 μl; from about 200 μl to about 50 μl, or from about 200 μl to about 100 μl. 
     
     
         14 . The method according to  claim 11 , wherein the volume of the application fluid per nostril ranges from about 150 μl to about 100 μl. 
     
     
         15 . The method according to  claim 10 , wherein said total amount is provided by administration to one nostril. 
     
     
         16 . The method according to  claim 10 , wherein the application fluid is water or an aqueous saline solution. 
     
     
         17 . The method according to  claim 16 , wherein the application fluid is an aqueous saline solution. 
     
     
         18 . The method according to  claim 17 , wherein the aqueous saline solution is a 0.9% (weight/volume) saline solution. 
     
     
         19 . The method according to  claim 10 , wherein the dosage form comprises at least one dosing unit, wherein the dosing unit comprises the total amount or half of the total amount of the naloxone or the pharmaceutically acceptable salt thereof dissolved in the application fluid, wherein
 the dosage form comprises one dosing unit and the dosing unit comprises the total amount of the naloxone or the pharmaceutically acceptable salt thereof when the total amount of the naloxone or the pharmaceutically acceptable salt thereof is provided by administration to one nostril; or   the dosage form comprises two dosing units and each dosing unit comprises half of the total amount of the naloxone or the pharmaceutically acceptable salt thereof when the total amount of the naloxone or the pharmaceutically acceptable salt thereof is provided by administration to two nostrils.   
     
     
         20 . The method according to  claim 19 , wherein the dosage form is for single use. 
     
     
         21 . The method according to  claim 19 , wherein the dosage form comprises at least one dosing unit and is for multiple uses. 
     
     
         22 . The method according to  claim 19 , wherein the dosage form comprises at least two dosing units, and is for multiple uses. 
     
     
         23 . The method according to  claim 10 , wherein the dosage form is a nasal spray, a nasal mucoadhesive dosage form, or a Mucosal Atomizer Device. 
     
     
         24 . The method according to  claim 10 , wherein the dosage form comprises naloxone or the pharmaceutically acceptable salt thereof as the only pharmaceutically active compound in the dosage form. 
     
     
         25 . The method according to  claim 10 , wherein the at least one symptom is selected from the group consisting of respiratory depression; altered level consciousness; miotic pupils; hypoxemia; acute lung injury, postoperative opioid respiratory depression, and aspiration pneumonia. 
     
     
         26 . The method according to  claim 10 , wherein said total amount is re-administered during an initial titration period in order to provide for an effective amount of naloxone. 
     
     
         27 . The method according to  claim 10 , wherein the dosage form is administered in combination with an intramuscular and/or intravenous dosage form comprising naloxone or a pharmaceutically acceptable salt thereof.