Formulation and Use and Manufacture Thereof

Abstract

This invention relates to a liquid pharmaceutical formulation for delivering nicotine to a subject. This invention also relates to a method and a system for delivering nicotine as well as manufacturing and use of said liquid pharmaceutical formulation.

1 . A method for delivering nicotine to a subject, the method comprising the steps of: 
 (a) administering a liquid pharmaceutical composition comprising nicotine into the oral cavity of a subject by spraying, dropping or pipetting thereby providing oral transmucosal delivery of nicotine to the subject without chewing or sucking, said composition having an alkaline pH and further comprising one or more buffers in an amount sufficient to transiently increase the pH of liquid in the oral cavity of said subject by about 0.3 to about 4 pH units; and    (b) allowing the nicotine to be systematically absorbed by buccal uptake.    
   
   
       2 . The method of  claim 1 , wherein absorption of said nicotine results in a t max  of nicotine in venous blood of the subject after about 3 to 30 minutes.  
   
   
       3 . The method of  claim 1 , wherein absorption of said nicotine results in a t max  of nicotine in venous blood of the subject after about 3 to 20 minutes.  
   
   
       4 . The method of  claim 1 , wherein absorption of said nicotine results in a t max  of nicotine in venous blood of the subject after about 3 to 15 minutes.  
   
   
       5 . The method of  claim 1 , wherein administration of said composition is by spraying under the tongue.  
   
   
       6 . The method of  claim 1 , wherein said composition, following administration to a subject, transiently increases the pH of the liquid of the oral cavity by about 0.5 to about 2.5 pH units.  
   
   
       7 . The method of  claim 1 , wherein said one or more buffers is a carbonate of an alkali metal or of ammonium, a glycinate of an alkali metal or of ammonium, a phosphate of an alkali metal or of ammonium, a glycerophosphate of an alkali metal or of ammonium, an acetate of an alkali metal or of ammonium, a gluconate of an alkali metal or of ammonium, or a citrate of an alkali metal or of ammonium, or mixtures thereof.  
   
   
       8 . The method of  claim 1 , wherein the amount of nicotine administered to the oral cavity at each incidence of administration is about 0.05 to about 10 mg calculated as the free base form of nicotine.  
   
   
       9 . A method for obtaining reduction of the urge to use tobacco containing material in a subject, the method comprising the steps of: 
 (a) replacing some or all of the tobacco containing material with a liquid pharmaceutical composition comprising nicotine, said composition having an alkaline pH and further comprising one or more buffers in an amount sufficient to transiently increase the pH of liquid in the oral cavity of said subject by about 0.3 to about 4 pH units;    (b) administering the liquid pharmaceutical composition into the oral cavity of a subject by spraying, dropping or pipetting thereby providing oral transmucosal delivery of nicotine to said subject without chewing or sucking; and    (c) allowing the nicotine to be systematically absorbed by the subject.    
   
   
       10 . The method of  claim 9 , wherein the method reduces the urge to smoke.  
   
   
       11 . The method of  claim 10 , wherein the method provides a sense of smoking satisfaction without smoking.  
   
   
       12 . The method of  claim 9 , wherein absorption of said nicotine results in a t max  of nicotine in venous blood of the subject after about 3 to 30 minutes.  
   
   
       13 . The method of  claim 9 , wherein absorption of said nicotine results in a t max  of nicotine in venous blood of the subject after about 3 to 20 minutes.  
   
   
       14 . The method of  claim 9 , wherein absorption of said nicotine results in a t max  of nicotine in venous blood of the subject after about 3 to 15 minutes.  
   
   
       15 . The method of  claim 9 , wherein administration of said composition is by spraying under the tongue.  
   
   
       16 . The method of  claim 9 , wherein said composition, following administration to a subject, transiently increases the pH of the liquid of the oral cavity by about 0.5 to about 2.5 pH units.  
   
   
       17 . The method of  claim 9 , wherein said one or more buffers is a carbonate of an alkali metal or of ammonium, a glycinate of an alkali metal or of ammonium, a phosphate of an alkali metal or of ammonium, a glycerophosphate of an alkali metal or of ammonium, an acetate of an alkali metal or of ammonium, a gluconate of an alkali metal or of ammonium, or a citrate of an alkali metal or of ammonium, or mixtures thereof.  
   
   
       18 . The method of  claim 9 , wherein the method for obtaining reduction of the urge to use tobacco containing material is performed in combination with one or more additional methods for obtaining reduction of the urge to use tobacco containing material.  
   
   
       19 . The method of  claim 18 , wherein the method for obtaining reduction of the urge to use tobacco containing material is performed in combination with the administration of nicotine through chewing gums, nasal sprays, transdermal patches, inhaling devices, lozenges, tablets, parenteral means or methods, subcutaneous means, intravenous means, rectal means, vaginal means or transmucosal means.  
   
   
       20 . A method for treating a disease, the method comprising the steps of: 
 (a) administering a liquid pharmaceutical composition comprising nicotine into the oral cavity of a subject by spraying, dropping or pipetting thereby providing oral transmucosal delivery of nicotine to the subject without chewing or sucking, said composition having an alkaline pH and further comprising one or more buffers in an amount sufficient to transiently increase the pH of liquid in the oral cavity of said subject by about 0.3 to about 4 pH units; and    (b) allowing the nicotine to be systematically absorbed by buccal uptake, wherein the disease is selected from the group consisting of addiction to tobacco or nicotine, Alzheimer's disease, Crohn's disease, Parkinson's disease, Tourette's syndrome, ulcerative colitis, and weight control.