Delivery of drugs to mucosal surfaces

Abstract

Liquid pharmaceutical compositions for administration to a mucosal surface, including fentanyl and a pectin with a low degree of esterification are described. Such compositions gel, or can be adapted to gel, at the site of application in the absence of an extraneous source of divalent metal ions.

1 . A liquid pharmaceutical composition for administration to a mucosal surface comprising: 
 fentanyl,    a pectin that has a degree of esterification of less than 50%, and    an aqueous carrier,    wherein the composition gels or is adapted to gel at a site of application on the mucosal surface in the absence of an extraneous source of divalent metal ions.    
   
   
       2 . The composition of  claim 1 , wherein the pectin has a degree of esterification that is less than 35%.  
   
   
       3 . The composition of  claim 1 , wherein the mucosal surface is the mucosa of the vagina, the mucosa of the rectum, the mucosa of the back of the throat, the mucosa of the nasal cavity, and the mucosa of the eye.  
   
   
       4 . The composition of  claim 3 , wherein the mucosal surface is the mucosa of the nasal cavity.  
   
   
       5 . The composition of  claim 1 , wherein the composition is in a dosage form adapted for administration to the mucosal surface.  
   
   
       6 . The composition of  claim 5 , wherein the dosage form is selected from the group consisting of a free flowing system and a spray.  
   
   
       7 . The composition of  claim 1 , wherein the composition has a pH of 2 to 9.  
   
   
       8 . The composition of  claim 1 , wherein the pectin is present in a concentration of 1 g/L to 100 g/L.  
   
   
       9 . The composition of  claim 1 , wherein the pectin is present in a concentration of 1 g/L to 50 g/L.  
   
   
       10 . A method for treatment or prophylaxis of a disease, the method comprising administering a composition according to  claim 1  to a mucosal surface wherein the composition gels or is adapted to gel at a site of administration in the absence of an extraneous source of divalent metal ions.  
   
   
       11 . A pharmaceutical gel composition prepared by applying a liquid composition according to  claim 1  to a mucosal surface of a mammal in the absence of extraneous divalent metal ions.  
   
   
       12 . The pharmaceutical gel composition of  claim 11 , wherein the pectin has a degree of esterification of less than 35%.  
   
   
       13 . A kit comprising a composition according to  claim 1 , but the kit does not include a solution of divalent metal ions.  
   
   
       14 . The kit of  claim 13 , wherein the pectin has a degree of esterification that is less than 35%.  
   
   
       15 . The kit of  claim 13 , wherein the composition is in a dosage form adapted for administration to the mucosal surface.  
   
   
       16 . The kit of  claim 15 , wherein the dosage form is selected from the group consisting of a free flowing system and a spray.  
   
   
       17 . The kit of  claim 13 , wherein the composition has a pH of 2 to 9.  
   
   
       18 . The kit of  claim 13 , wherein the pectin is present in the composition in a concentration of 1 g/L to 100 g/L.  
   
   
       19 . The kit of  claim 13 , wherein the pectin is present in the composition in a concentration of 1 g/L to 50 g/L.  
   
   
       20 . A method of delivering fentanyl to a mucosal surface in a mammal comprising administering a liquid pharmaceutical composition according to  claim 1  to a mucosal surface of a mammal in the absence of extraneous divalent metal ions.  
   
   
       21 . The method of  claim 20 , wherein the pectin has a degree of esterification that is less than 35%.  
   
   
       22 . The method of  claim 20 , wherein the composition is in a dosage form adapted for administration to the mucosal surface.  
   
   
       23 . The method of  claim 22 , wherein the dosage form is selected from the group consisting of a free flowing system and a spray.  
   
   
       24 . The method of  claim 20 , wherein the composition has a pH of 2 to 9.  
   
   
       25 . The method of  claim 20 , wherein the pectin is present in the composition in a concentration of 1 g/L to 100 g/L.  
   
   
       26 . The method of  claim 20 , wherein the pectin is present in the composition in a concentration of 1 g/L to 50 g/L.  
   
   
       27 . A method of preparing a liquid pharmaceutical composition comprising mixing fentanyl, a pectin that has a degree of esterification of less than 50%, and a aqueous carrier to form a liquid composition that gels or is adapted to gel at a site of administration in the absence of divalent metal ions.  
   
   
       28 . The method of  claim 27 , wherein the pectin has a degree of esterification that is less than 35%.  
   
   
       29 . The method of  claim 27 , wherein the composition is in a dosage form adapted for administration to the mucosal surface.  
   
   
       30 . The method of  claim 29 , wherein the dosage form is selected from the group consisting of a free flowing system and a spray.  
   
   
       31 . The method of  claim 27 , wherein the composition has a pH of 2 to 9.  
   
   
       32 . The method of  claim 27 , wherein the pectin is present in the composition in a concentration of 1 g/L to 100 g/L.  
   
   
       33 . The method of  claim 27 , wherein the pectin is present in the composition in a concentration of 1 g/L to 50/L.