Method of enhancing absorptions of transmucosal administration formulations

Abstract

Disclosed is a method for enhancing absorption of a medicament that is suitable for administering transmucosally to a subject by providing an environment of the administration with a suitable pH. A medicament of propranolol suitably administered sublingually is provided. The medicament of propranolol can be used for treating cardiovascular diseases.

1 . A method for enhancing absorption of a medicament that is suitable for transmucosal administration to a subject, said method comprising providing an environment for the administration with a pH of about:  
       
         
           
             
               pH 
               = 
               
                 - 
                 
                   log 
                   ⁡ 
                   
                     ( 
                     
                       
                         Ka 
                         · 
                         
                           S 
                           i 
                         
                       
                       
                         S 
                         u 
                       
                     
                     ) 
                   
                 
               
             
           
         
         in which K a  is the ionization constant (dissociation constant) of the compound in water, S i  is the solubility of the ionized form of the compound, and S u  is the solubility of the non-ionized form of the compound.  
       
     
     
         2 . The method of  claim 1 , wherein the pH of the environment is provided by a buffering agent in the medicament.  
     
     
         3 . The method of  claim 2 , wherein the environment of administration is in the oral mucosa.  
     
     
         4 . The method of  claim 3 , wherein the environment of administration is a sublingual environment.  
     
     
         5 . The method of  claim 1 , wherein the medicament is propanolol.  
     
     
         6 . The method of  claim 1 , wherein the medicament is selected from the group consisting of scopolamine and estradiol.  
     
     
         7 . A method for enhancing absorption of a medicament comprising propranolol or a pharmaceutically acceptable form thereof that is administered transmucosally to a subject, comprising providing an environment for the administration with a pH in the range from about 7.2 to about 7.8.  
     
     
         8 . The method of  claim 7 , wherein the medicament is administered sublingually.  
     
     
         9 . The method of  claim 8 , wherein the pH is about 7.6.  
     
     
         10 . The method of  claim 8 , wherein the pharmaceutically acceptable form is an acidic salt.  
     
     
         11 . The method of  claim 10 , wherein the salt is hydrochloride.  
     
     
         12 . The method of  claim 8 , wherein the medicament comprises a buffering agent.  
     
     
         13 . The method of  claim 12 , wherein the buffering agent is a phosphate buffer.  
     
     
         14 . The method of  claim 13 , wherein the buffering agent is disodium hydrogen phosphate, sodium dihydrogen phosphate or a combination thereof.  
     
     
         15 . A medicament suitable for transmucosal administration to a subject, comprising an effective amount of propranolol or a pharmaceutically acceptable form thereof, and a pharmaceutically acceptable carrier, wherein the medicament provides an environment of the administration with a pH of about 7.2 to about 7.8.  
     
     
         16 . The medicament of  claim 15 , wherein the pH is from about 7.6.  
     
     
         17 . The medicament of  claim 15 , wherein the pharmaceutically acceptable form is a salt.  
     
     
         18 . The medicament of  claim 17 , wherein the salt is hydrochloride.  
     
     
         19 . The medicament of  claim 15 , wherein the medicament comprises a buffering agent.  
     
     
         20 . The medicament of  claim 19 , wherein the buffering agent is a phosphate buffer.  
     
     
         21 . The medicament of  claim 20 , wherein the buffering agent is disodium hydrogen phosphate, sodium dihydrogen phosphate or a combination thereof.  
     
     
         22 . The medicament of  claim 15 , wherein the medicament is formulated as a tablet.  
     
     
         23 . The medicament of  claim 22 , wherein the tablet contains propranolol of from about 20 mg to about 80 mg.  
     
     
         24 . A method for treating cardiovascular diseases of a subject comprising transmucosal administration of a therapeutically effective amount of propanolol to the subject in an environment with a pH range of about 7.2 to about 7.8.  
     
     
         25 . The method of  claim 24 , wherein the administration is performed sublingually, and the pH is about 7.6.