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 about 60 mcg 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 oral mucosa of the patient, and
 wherein the method achieves a T max  between 0.98 hour and 3.95 hours, a C max  between 73.42 ng/L and 253.14 ng/L, and an AUCINF_obs between 293.67 hr*ng/L and 2195.38 hr*ng/L.   
     
     
         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 T max  is between 1 hour and 2 hours. 
     
     
         6 . The method of  claim 1 , wherein the T max  is between 1 hour and 1.5 hours. 
     
     
         7 . The method of  claim 1 , wherein the T max  is between 1.45 hours and 2 hours. 
     
     
         8 . The method of  claim 1 , wherein the C max  is between 93.67 ng/L and 206.42 ng/L. 
     
     
         9 . The method of  claim 1 , wherein the C max  is between 105.84 ng/L and 186.40 ng/L. 
     
     
         10 . The method of  claim 1 , wherein the C max  is between 113.35 ng/L and 154.79 ng/L. 
     
     
         11 . The method of  claim 1 , wherein the C max  is between 127.30 ng/L and 144.27 ng/L. 
     
     
         12 . The method of  claim 1 , wherein the AUCINF_obs is between 369.07 hr*ng/L and 1064.08 hr*ng/L. 
     
     
         13 . The method of  claim 1 , wherein the AUCINF_obs is between 377.98 hr*ng/L and 877.63 hr*ng/L. 
     
     
         14 . The method of  claim 1 , wherein the AUCINF_obs is between 428.64 hr*ng/L and 807.14 hr*ng/L. 
     
     
         15 . The method of  claim 1 , wherein the AUCINF_obs is between 537.29 hr*ng/L and 691.00 hr*ng/L. 
     
     
         16 . A pharmaceutical delivery system, comprising:
 means for achieving a T max  between 0.98 hour and 3.95 hours, a C max  between 73.42 ng/L and 253.14 ng/L, and an AUCINF_obs between 293.67 hr*ng/L and 2195.38 hr*ng/L;   means for adhering the pharmaceutical delivery system to human oral mucosa; and   wherein the pharmaceutical delivery system comprises 60 mcg dexmedetomidine or a pharmaceutically acceptable salt thereof.   
     
     
         17 . The pharmaceutical delivery system of  claim 16 , wherein the T max  is between 1 hour and 2 hours. 
     
     
         18 . The pharmaceutical delivery system of  claim 16 , wherein the T max  is between 1 hour and 1.5 hours. 
     
     
         19 . The pharmaceutical delivery system of  claim 16 , wherein the T max  is between 1.45 hours and 2 hours. 
     
     
         20 . The pharmaceutical delivery system of  claim 16 , wherein the C max  is between 93.67 ng/L and 206.42 ng/L. 
     
     
         21 . The pharmaceutical delivery system of  claim 16 , wherein the C max  is between 105.84 ng/L and 186.40 ng/L. 
     
     
         22 . The pharmaceutical delivery system of  claim 16 , wherein the C max  is between 113.35 ng/L and 154.79 ng/L. 
     
     
         23 . The pharmaceutical delivery system of  claim 16 , wherein the C max  is between 127.30 ng/L and 144.27 ng/L. 
     
     
         24 . The pharmaceutical delivery system of  claim 16 , wherein the AUCINF_obs is between 369.07 hr*ng/L and 1064.08 hr*ng/L. 
     
     
         25 . The pharmaceutical delivery system of  claim 16 , wherein the AUCINF_obs is between 377.98 hr*ng/L and 877.63 hr*ng/L. 
     
     
         26 . The pharmaceutical delivery system of  claim 16 , wherein the AUCINF_obs is between 428.64 hr*ng/L and 807.14 hr*ng/L. 
     
     
         27 . The pharmaceutical delivery system of  claim 16 , wherein the AUCINF_obs is between 537.29 hr*ng/L and 691.00 hr*ng/L. 
     
     
         28 . A method of treating agitation associated with dementia, schizophrenia, or bipolar I or II disorder in a human subject, comprising administering the pharmaceutical delivery system of  claim 16 . 
     
     
         29 . The method of  claim 28 , wherein the pharmaceutical delivery system is administered sublingually. 
     
     
         30 . The method of  claim 28 , wherein the pharmaceutical delivery system is administered buccally.