Film formulations containing dexmedetomidine and methods of producing them

Abstract

Disclosed herein is a self-supporting, dissolvable, film containing dexmedetomidine or a pharmaceutically acceptable salt thereof. The film is administered orally to treat various conditions, particularly agitation, by transmucosal delivery of the active agent.

What is claimed is: 
     
         1 . An oromucosal formulation comprising:
 dexmedetomidine or a pharmaceutically acceptable salt thereof; and   at least one water-soluble polymer;   wherein the at least one water-soluble polymer is selected from the group consisting of hydroxypropyl cellulose, hydroxypropyl methylcellulose, hydroxyethyl cellulose, carboxy methylcellulose, methylcellulose, polyethylene oxide (PEO), and mixtures thereof; and   wherein the oromucosal formulation provides at least 45.6% bioavailability when administered to an oral mucosa of an animal subject that is a male New Zealand White  Oryctolagus cuniculus  with an initial body weight between 2.9 kg and 3.9 kg.   
     
     
         2 . The oromucosal formulation of  claim 1 , wherein the oromucosal formulation provides at least 52.2% bioavailability when administered to the animal subject. 
     
     
         3 . The oromucosal formulation of  claim 1 , wherein the oromucosal formulation provides at least 63.4% bioavailability when administered to the animal subject. 
     
     
         4 . The oromucosal formulation of  claim 1 , wherein the oromucosal formulation provides at least 70.5% bioavailability when administered to the animal subject. 
     
     
         5 . The oromucosal formulation of  claim 1 , wherein the oromucosal formulation provides a C max /dose ratio no lower than 0.119 [(ng/mL)/(μg/kg)] in more than 50% of the animal subjects. 
     
     
         6 . The oromucosal formulation of  claim 1 , wherein the oromucosal formulation provides a C max /dose ratio no lower than 0.119 [(ng/mL)/(μg/kg)] in at least 75% of the animal subjects. 
     
     
         7 . The oromucosal formulation of  claim 1 , wherein the oromucosal formulation provides a C max /dose ratio no lower than 0.119 [(ng/mL)/(μg/kg)]. 
     
     
         8 . A method of treating agitation in a human patient comprising administering to the human patient an oromucosal formulation;
 wherein the oromucosal formulation comprises an effective amount of dexmedetomidine or a pharmaceutically acceptable salt thereof and at least one water-soluble polymer;   wherein the at least one water-soluble polymer is selected from the group consisting of hydroxypropyl cellulose, hydroxypropyl methylcellulose, hydroxyethyl cellulose, carboxy methylcellulose, methylcellulose, polyethylene oxide (PEO), and mixtures thereof; and   wherein the oromucosal formulation provides at least 45.6% bioavailability when administered to an oral mucosa of an animal subject with a body-weight adjusted dose, wherein the animal subject is a male New Zealand White  Oryctolagus cuniculus  with an initial body weight between 2.9 kg and 3.9 kg.   
     
     
         9 . The method of  claim 8 , wherein the oromucosal formulation provides at least 52.2% bioavailability when administered to the animal subject. 
     
     
         10 . The method of  claim 8 , wherein the oromucosal formulation provides at least 63.4% bioavailability when administered to the animal subject. 
     
     
         11 . The method of  claim 8 , wherein the oromucosal formulation provides at least 70.5% bioavailability when administered to the animal subject. 
     
     
         12 . The method of  claim 8 , wherein the oromucosal formulation provides a C max /dose ratio no lower than 0.119 [(ng/mL)/(μg/kg)] in more than 50% of the animal subjects. 
     
     
         13 . The method of  claim 8 , wherein the oromucosal formulation provides a C max /dose ratio no lower than 0.119 [(ng/mL)/(μg/kg)] in at least 75% of the animal subjects. 
     
     
         14 . The method of  claim 8 , wherein the oromucosal formulation provides a C max /dose ratio no lower than 0.119 [(ng/mL)/(μg/kg)].