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 . A method of treating agitation in a patient comprising administering a film comprising dexmedetomidine or a pharmaceutically acceptable salt thereof, water-soluble hydroxypropyl cellulose polymers having molecular weight of about 40,000 daltons, about 140,000 daltons, and about 370,000 daltons and a water-soluble polyethylene oxide polymer having a molecular weight of about 600,000 daltons, to the oral mucosa of the patient, wherein the method achieves a C max  of about 73 ng/L to about 253 ng/L, wherein said dexmedetomidine or pharmaceutically acceptable salt thereof is present in the film in an amount of about 60 micrograms. 
     
     
         2 . The method of  claim 1 , wherein the patient is a human. 
     
     
         3 . The method of  claim 1 , wherein the administration to the oral mucosa of the patient is sublingual administration. 
     
     
         4 . The method of  claim 1 , wherein the administration to the oral mucosa of the patient is buccal administration. 
     
     
         5 . The method of  claim 1 , wherein the C max  is about 73 ng/L. 
     
     
         6 . The method of  claim 1 , wherein the C max  is about 253 ng/L. 
     
     
         7 . The method of  claim 1 , wherein the C max  is about 132 ng/L. 
     
     
         8 . The method of  claim 1 , wherein the method achieves T max  at about 1 to about 4 hours. 
     
     
         9 . The method of  claim 1 , wherein the method achieves T max  at about 1 hour. 
     
     
         10 . The method of  claim 1 , wherein the method achieves T max  at about 1.5 hours. 
     
     
         11 . The method of  claim 1 , wherein the method achieves T max  at about 2 hours. 
     
     
         12 . The method of  claim 1 , wherein the method achieves T max  at about 4 hours. 
     
     
         13 . A film comprising dexmedetomidine or a pharmaceutically acceptable salt thereof, wherein the film achieves a C max  of about 73 ng/L to about 253 ng/L, wherein the dexmedetomidine or pharmaceutically acceptable salt thereof is present in an amount of about 60 micrograms, and wherein the film further comprises water-soluble hydroxypropyl cellulose polymers having molecular weight of about 40,000 daltons, about 140,000 daltons, and about 370,000 daltons and a water-soluble polyethylene oxide polymer having a molecular weight of about 600,000 daltons. 
     
     
         14 . The film of  claim 13 , wherein the C max  is about 73 ng/L. 
     
     
         15 . The film of  claim 13 , wherein the C max  is about 253 ng/L. 
     
     
         16 . The film of  claim 13 , wherein the C max  is about 132 ng/L. 
     
     
         17 . The film of  claim 13 , wherein the method achieves T max  at about 1 to about 4 hours. 
     
     
         18 . The film of  claim 13 , wherein the method achieves T max  at about 1 hour. 
     
     
         19 . The film of  claim 13 , wherein the method achieves T max  at about 1.5 hours. 
     
     
         20 . The film of  claim 13 , wherein the method achieves T max  at about 2 hours. 
     
     
         21 . The film of  claim 13 , wherein the method achieves T max  at about 4 hours. 
     
     
         22 . The film of  claim 13 , wherein the film has a thickness of about 20 micrometers to about 200 micrometers. 
     
     
         23 . The film of  claim 13 , wherein the film has a thickness of about 20 micrometers to about 200 micrometers and covers an area (width×length) of about 100 mm 2  to about 300 mm 2 . 
     
     
         24 . The film of  claim 13 , wherein the film has a disintegration time of about 60 seconds to about 180 seconds. 
     
     
         25 . The film of  claim 13 , wherein the film is completely dissolvable in oral mucosal fluid in about 1 minute to about 5 minutes.