Therapeutical composition containing apomorphine as active ingredient

Abstract

A pharmaceutical composition contains apomorphine as the active pharmaceutical ingredient, a water-miscible co-solvent, an antioxidant, and water. The solution has a pH greater than 4. The pharmaceutical composition is suitable for parenteral administration for the treatment of Parkinson's disease. The process for the manufacture of the pharmaceutical composition includes weighing the apomorphine and introducing it into a container with the co-solvent and the antioxidant under agitation until complete dissolution takes place.

1 - 14 . (canceled) 
     
     
         15 . A method of administering a pharmaceutical composition to a patient in need thereof, the method comprising:
 administering the pharmaceutical composition by parenteral route,   wherein the pharmaceutical composition includes:   i) apomorphine as an active substance;   ii) a water miscible co-solvent;   iii) an antioxidant; and   iv) water; and   wherein a pH of the pharmaceutical composition is greater than 4.   
     
     
         16 . A method of reducing “off episodes” in a patient with advanced Parkinson's disease comprising administering the pharmaceutical composition according to  claim 15 . 
     
     
         17 - 18 . (canceled) 
     
     
         19 . The method according to  claim 15 , wherein an amount of the active substance is between about 10 to 70 mg/ml. 
     
     
         20 . The method according to  claim 15 , wherein an amount of the water miscible co-solvent is between 0.1 to 80% (w:w) of the pharmaceutical composition. 
     
     
         21 . The method according to  claim 15 , wherein the water miscible co-solvent is selected from the group consisting of an alcohol, a polyol, and a polyether or a mixture thereof. 
     
     
         22 . The method according to  claim 15 , wherein the co-solvent is selected from a diol, a triol, a cyclodextrin derivative, a polyethylene glycol, and a polyethylene glycol derivative or a mixture thereof. 
     
     
         23 . The method according to  claim 15 , wherein the antioxidant is selected from the group consisting of an acid, a salt thereof, a vitamin, a vitamin derivative, an amino acid, a sulphite, and a phenolic free radical scavenger. 
     
     
         24 . The method according to  claim 15 , wherein the antioxidant is selected from the group consisting of ascorbic acid and sodium metabisulfite. 
     
     
         25 . The method according to  claim 15 , wherein the pharmaceutical composition further comprises a surfactant. 
     
     
         26 . The method according to  claim 25 , wherein the surfactant has a hydrophile-lipophile balance (HLB) between 8 and 20. 
     
     
         27 . The method according to  claim 25 , wherein the surfactant is selected from the group consisting of a polyoxyethylene sorbitan fatty ester, a polyethylene glycol derivative, and a poloxamer. 
     
     
         28 . The method according to  claim 15 , wherein an apomorphine: co-solvent ratio (w:w) is between 1:0.1 to 1:40. 
     
     
         29 . The method according to  claim 15 , wherein the pH of the composition is between 4 and 7. 
     
     
         30 . The method according to  claim 15 , wherein the composition further comprises a pH modifier. 
     
     
         31 . The method according to  claim 30 , wherein the pH modifier is selected from the group consisting of sodium hydroxide, sodium bicarbonate, potassium hydroxide, and magnesium hydroxide or a mixture thereof.