New alfentanil composition for the treatment of acute pain

Abstract

There is provided pharmaceutical compositions for the treatment of pain e.g. short-term pain, which compositions comprise a mixture comprising: (a) microparticles of alfentanil, or a pharmaceutically acceptable salt thereof, which microparticles are presented on the surfaces of larger carrier particles; (b) a water-soluble weak base; and (c) a compound which is a weak acid, which acid is presented in intimate mixture with the microparticles of alfentanil or salt thereof. The composition may further comprise a disintegrant. The acid is preferably citric acid.

1 . A pharmaceutical composition suitable for sublingual delivery which comprises a mixture comprising:
 (a) microparticles of alfentanil, or a pharmaceutically acceptable salt thereof, which microparticles are presented on the surfaces of larger carrier particles;   (b) a water-soluble weak base; and   (c) a compound which is a weak acid, which acid is presented in intimate mixture with the microparticles of alfentanil or salt thereof.   
     
     
         2 . A formulation as claimed in  claim 1 , wherein particles of weakly acidic material are presented within the carrier particles, such that said carrier particles comprise a composite of:
 (i) said acid material; and   (ii) another carrier particle material.   
     
     
         3 . A composition as claimed in  claim 1 , wherein the particles of weakly acidic material are presented upon the surfaces of the carrier particles. 
     
     
         4 . A composition as claimed in  claim 1 , wherein the acid is citric acid. 
     
     
         5 . A composition as claimed in  claim 1 , wherein the water-soluble weak base comprises a phosphate, such as trisodium phosphate. 
     
     
         6 . A composition as claimed in  claim 1 , wherein the carrier particles comprise mannitol. 
     
     
         7 . A pharmaceutical composition as claimed in  claim 1 , which further comprises a disintegrant. 
     
     
         8 . A composition as claimed in  claim 7 , wherein the disintegrant is a superdisintegrant selected from croscarmellose sodium, sodium starch glycolate, crosslinked polyvinylpyrrolidone or a mixture thereof. 
     
     
         9 . A composition as claimed in  claim 1  which is in the form of a tablet suitable for sublingual administration. 
     
     
         10 . A process for the preparation of a composition of  claim 1 , which comprises dry mixing carrier particles with alfentanil or salt thereof. 
     
     
         11 . A process for the preparation of a sublingual tablet of  claim 1 , which comprises directly compressing or compacting said composition. 
     
     
         12 . A method of treatment of pain, which method comprises administration of a composition of  claim 1  to a person suffering from, or susceptible to pain. 
     
     
         13 . A composition of  claim 1  for use in a method of treatment of pain. 
     
     
         14 . The use of a composition as defined in  claim 1  for the manufacture of a medicament for a method of treatment of pain. 
     
     
         15 . A method as claimed in  claim 12 , wherein the pain is moderate to severe pain. 
     
     
         16 . A composition as claimed in  claim 13 , wherein the pain is moderate to severe pain. 
     
     
         17 . A use as claimed in  claim 14 , wherein the pain is moderate to severe pain. 
     
     
         18 . A method as claimed in  claim 15 , wherein the treatment is short term. 
     
     
         19 . A composition as claimed in  claim 16 , wherein the treatment is short term. 
     
     
         20 . A use as claimed in  claim 17 , wherein the treatment is short term. 
     
     
         21 . A method as claimed in  claim 15 , wherein the pain is associated with a diagnostic, a surgical or a care-related procedure. 
     
     
         22 . A composition as claimed in  claim 16 , wherein the pain is associated with a diagnostic, a surgical or a care-related procedure. 
     
     
         23 . A method as claimed in  claim 15 , wherein the composition is administered not more than about 20 minutes prior to the procedure. 
     
     
         24 . A composition as claimed in  claim 16  wherein the composition is administered not more than about 20 minutes prior to the procedure. 
     
     
         25 . A method of treatment of pain as claimed in  claim 12 , which method comprises sublingual administration to a human patient in need of treatment of a pharmaceutical composition comprising between about 30 μg and about 3,000 μg of alfentanil or a pharmaceutically acceptable salt thereof, wherein said administration gives rise to a plasma concentration-time curve after said administration that posseses:
 (I) a t max  (time to maximum plasma concentration) that is between about 10 and about 25 minutes after said administration; and/or 
 (II) a t last  (time to last measurable plasma concentration) that is not more than about 300 minutes after said administration; and, optionally, 
 (III) a C max  (maximum plasma concentration) that is between about 10 and about 100 ng per mL of plasma. 
 
     
     
         26 . A method as claimed in  claim 25  which comprises administration of a pharmaceutical composition suitable for sublingual delivery which comprises a mixture comprising:
 (a) microparticles of alfentanil, or a pharmaceutically acceptable salt thereof, which microparticles are presented on the surfaces of larger carrier particles; 
 (b) a water-soluble weak base; and 
 (c) a compound which is a weak acid, which acid is presented in intimate mixture with the microparticles of alfentanil or salt thereof.