Pharmaceutical compositions

Abstract

This invention provides a composition for the intranasal delivery of fentanyl or a pharmaceutically acceptable salt thereof to an animal comprising an aqueous solution of fentanyl or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable additive selected from (i) a pectin and (ii) a poloxamer and chitosan or a salt or derivative thereof; provided that when the composition comprises a pectin it is substantially free of divalent metal ions; and which, in comparison to a simple aqueous solution of fentanyl administered intranasally at the same dose, provides a peak plasma concentration of fentanyl (C max ) that is from 10 to 80% of that achieved using a simple aqueous solution of fentanyl administered intranasally at an identical fentanyl dose.

We claim:  
     
         1 . A composition for the intranasal delivery of fentanyl or a pharmaceutically acceptable salt thereof to an animal comprising an aqueous solution of 
 fentanyl or a pharmaceutically acceptable salt thereof and    a pharmaceutically acceptable additive selected from (i) a pectin and (ii) a poloxamer and chitosan or a salt or derivative thereof;    provided that when the composition comprises a pectin it is substantially free of divalent metal ions;    and which, in comparison to a simple aqueous solution of fentanyl administered intranasally at the same dose, provides a peak plasma concentration of fentanyl (C max ) that is from 10 to 80% of that achieved using a simple aqueous solution of fentanyl administered intranasally at an identical fentanyl dose.    
     
     
         2 . A composition according to  claim 1 , which, in comparison to a simple aqueous solution of fentanyl administered intranasally at the same dose, provides a peak plasma concentration of fentanyl (C max ) that is from 30 to 70% of that achieved using a simple aqueous solution of fentanyl administered intranasally at an identical fentanyl dose.  
     
     
         3 . A composition according to  claim 1 , comprising a pharmaceutically acceptable salt of fentanyl.  
     
     
         4 . A composition according to  claim 3 , wherein the pharmaceutically acceptable salt of fentanyl is fentanyl citrate.  
     
     
         5 . A composition according to  claim 1 , wherein the additive is a pectin.  
     
     
         6 . A composition according to  claim 5 , wherein the pectin has a DE value of from 7 to 30%.  
     
     
         7 . A composition according to  claim 5 , wherein the concentration of pectin is from 5 to 25 mg/ml.  
     
     
         8 . A composition according to  claim 5  that is at least 99% free of divalent metal ions.  
     
     
         9 . A composition according to  claim 5  having an osmolality of from 0.25 to 0.35 osmol/kg.  
     
     
         10 . A composition according to  claim 5  having a pH of from 3.4 to 5.0.  
     
     
         11 . A composition according to  claim 1 , wherein the additive is a poloxamer and chitosan or a salt or derivative thereof.  
     
     
         12 . A composition according to  claim 11 , wherein the chitosan or salt derivative thereof is chitosan glutamate.  
     
     
         13 . A composition according to  claim 11 , wherein the concentration of poloxamer is from 80 to 120 mg/ml and the concentration of chitosan or a salt or derivative thereof is from 1 to 10 mg/ml (expressed as chitosan base).  
     
     
         14 . A composition according to  claim 11  having an osmolality of from 0.4 to 0.7 osmol/kg.  
     
     
         15 . A composition according to  claim 11  having a pH of from 3.0 to 5.0.  
     
     
         16 . A composition according to  claim 1 , wherein the concentration of fentanyl or a pharmaceutically acceptable salt thereof is from 0.2 to 15 mg/ml (expressed as fentanyl base).  
     
     
         17 . A composition according to  claim 1  which is adapted to be delivered to the nose in the form of drops or as a spray.  
     
     
         18 . A composition according to  claim 1  for use in the treatment or prevention of acute or chronic pain.  
     
     
         19 . The use of a pharmaceutically acceptable additive selected from 
 (i) a pectin and    (ii) a poloxamer and chitosan or a salt or derivative thereof,    in the manufacture of a medicament for the intranasal delivery of fentanyl or a pharmaceutically acceptable salt thereof to an animal in need thereof, which medicament is adapted to provide a peak plasma concentration of fentanyl (C max ) that is from 10 to 80% of that achieved using a simple aqueous solution of fentanyl administered intranasally at an identical fentanyl dose.    
     
     
         20 . Use according to  claim 19  for the manufacture of a medicament for the treatment or prevention of acute or chronic pain.  
     
     
         21 . A method for the treatment or prevention of acute or chronic pain, comprises an intranasal delivery of a composition according to  claim 1  to a patient.  
     
     
         22 . A spray device loaded with a composition according to  claim 1 .  
     
     
         23 . A process for preparing a composition according to  claim 1  comprising mixing fentanyl or a pharmaceutically acceptable salt thereof with the pharmaceutically acceptable additive in water.