Oromucosal Apomorphine Compositions

Abstract

An oromucosal solution comprising about 1-8% (w/v) apomorphine or a pharmaceutical acceptable salt thereof solubilised in a non-aqueous carrier containing at least about 50% (v/v) of propylene glycol. A small volume (25-250 μL) of said solution containing about 1-12 mg apomorphine may be administered upon demand to treat motor fluctuations during off periods in patients suffering from Parkinson's disease. The solution may also be used for the treatment of sexual dysfunction.

1 . A solution for oromucosal delivery comprising about 1-8% (w/v) apomorphine or a pharmaceutical acceptable salt thereof solubilised in a non-aqueous carrier containing at least about 50% (v/v) of propylene glycol. 
     
     
         2 . The oromucosal solution of  claim 1 , further comprising an antioxidant. 
     
     
         3 . The oromucosal solution of  claim 1  or  claim 2 , further comprising one or more auxiliary solvents selected from ethanol, isopropanol and polyhydroxysolvents. 
     
     
         4 . The oromucosal solution of  claim 3 , wherein said polyhydroxysolvents are selected from glycerol, polyethylene glycol 200-600 and alkoxypolyethylene glycols. 
     
     
         5 . The oromucosal solution of any preceding claim, the solution having a viscosity less than about 200 mPa·s measured at 22° C. 
     
     
         6 . The oromucosal solution of any preceding claim, wherein the solution is free or substantially free of divalent cations. 
     
     
         7 . The oromucosal solution of  claim 1 , consisting essentially of: 
       
         
           
                 
                 
                 
               
                     
                     
                 
                     
                   Apomorphine 
                   1-8% (w/v) 
                 
                     
                   Ethanol 
                   0 or 1-50% (v/v) 
                 
                     
                   Ascorbic acid 
                   0 or 0.1-5% (w/v) 
                 
                     
                   Antioxidant 
                   q.s. 
                 
                     
                   Flavouring agent 
                   q.s. 
                 
                     
                   Sweetener 
                   q.s. 
                 
                     
                   Propylene glycoL 
                   Balance - up to 100% (v/v). 
                 
                     
                     
                 
             
                
               
               
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         8 . The oromucosal solution of any of the preceding claims, for use in the treatment of Parkinson's disease, alleviating akinesia or dyskinesia, or the treatment of male or female sexual dysfunction. 
     
     
         9 . The oromucosal solution of any preceding claim, for use in the treatment of patients who are receiving another treatment for Parkinson's disease during “off-periods” or as a rescue therapy. 
     
     
         10 . The oromucosal solution of  claim 8  or  claim 9 , wherein said solution is co-administered with an anti-emetic agent. 
     
     
         11 . The oromucosal solution of  claim 8 ,  claim 9  or  claim 10 , wherein the solution is administered to the oromucosal membrane in a dose of about 25-250 μl in the form of a free liquid. 
     
     
         12 . The oromucosal solution of  claim 11 , wherein said dose comprises about 1-12 mg of apomorphine. 
     
     
         13 . The oromucosal solution of  claim 11  or  claim 12 , wherein said solution is administered with a dosage interval of at least about 2 hours. 
     
     
         14 . The oromucosal solution of any of  claims 8 - 13 , wherein said solution is administered buccally or gingivally. 
     
     
         15 . The oromucosal solution of any of  claims 8 - 14 , for use in the treatment of off-periods in patients with Parkinson's disease, wherein the solution is administered in a volume of about 25-250 μL, containing about 1-12 mg of apomorphine, at intervals of about 2-12 hours during the day. 
     
     
         16 . The oromucosal solution of  claim 15 , wherein the solution is administered in a volume of about 25-150 μL, containing about 2-12 mg of apomorphine, at intervals of about 2-8 hours during the day. 
     
     
         17 . A dosage form containing an amount of the oromucosal solution of any of  claims 1 - 15 , wherein said dosage form is adapted to dispense upon actuation a predetermined volume of about 25-250 μl of said solution as a free liquid containing about 1-12 mg apomorphine. 
     
     
         18 . The dosage form of  claim 17 , wherein the dosage form comprises a dosage pen or pipette or a device that is adapted to dispense said predetermined volume in the form of a spray or one or more drops. 
     
     
         19 . The dosage form of  claim 17  or  claim 18 , wherein said solution is stored in the dosage form under an inert (non-oxidising) atmosphere. 
     
     
         20 . The dosage form of  claim 17 ,  claim 18  or  claim 19 , wherein said solution is stored in the dosage form in the dark. 
     
     
         21 . A method of treating motor fluctuations in a subject receiving treatment for Parkinson's disease, the method comprising administering oromucosally to the subject in need thereof during an off period a dose of about 25-250 μL of a solution comprising about 1-8% (w/v) apomorphine or a pharmaceutically acceptable salt thereof in the form of a free liquid. 
     
     
         22 . The method of  claim 21 , wherein said solution is administered to said subject with a dosage interval of at least 2 hours. 
     
     
         23 . The method of  claim 21 , wherein said solution is administered to the subject in the form of a spray or drops or by a dosage pen. 
     
     
         24 . The method of  claim 21 , wherein said solution is administered buccally or gingivally. 
     
     
         25 . The method of  claim 21 , wherein the solution is a solution according to  claim 1 .