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.

What is claimed is: 
     
         1 . A pharmaceutical composition for parenteral administration by injection in the form of a solution comprising
 i) apomorphine as the active substance;   ii) a water miscible co-solvent;   iii) an antioxidant; and   iv) water,   
       wherein the pH of the composition is greater than 4, 
       wherein the amount of the active ingredient is between 10-65 mg/ml. 
     
     
         2 . The composition according to  claim 1  wherein the amount of co-solvent alone or in mixture thereof is between 0.2 to 70%. 
     
     
         3 . The composition according to  claim 1  wherein the co-solvent is selected from polyols and polyethers or a mixture thereof. 
     
     
         4 . The composition according to  claim 1  wherein the co-solvent is selected from diols, triols, cyclodextrin derivatives, polyethylene glycols and polyethylene glycol derivatives or a mixture thereof. 
     
     
         5 . The composition according to  claim 1  wherein the antioxidant is selected from acids and their salts, and sulfites. 
     
     
         6 . The composition according to  claim 1  wherein the antioxidant is selected from ascorbic acid and sodium metabisulfite. 
     
     
         7 . The composition according to  claim 1  wherein a surfactant is present in the composition. 
     
     
         8 . The composition of  claim 7  wherein the surfactant has a HLB between 12 to 17. 
     
     
         9 . The composition of  claim 8  wherein the surfactant is selected from polyoxyethylene sorbitan fatty ester(s) or polyethylene glycol derivatives or poloxamers. 
     
     
         10 . The composition according to  claim 1  wherein the apomorphine:co-solvent ratio (w:w) is between 1:0.2 and 1:30. 
     
     
         11 . The composition according to  claim 1  wherein the pH of the composition is between 5 and 7. 
     
     
         12 . The composition according to  claim 1  wherein a pH modifier is present in the composition. 
     
     
         13 . The composition according to  claim 12  wherein the pH modifier is selected from sodium hydroxide, sodium bicarbonate, potassium hydroxide, magnesium hydroxide, hydrochloric acid or a mixture thereof. 
     
     
         14 . The composition according to  claim 1  which is suitable to be administered by a subcutaneous infusion. 
     
     
         15 . The composition according to  claim 1  for use as medicament intended to reduce “off episodes” in patients with advanced Parkinson's disease. 
     
     
         16 . The composition according to  claim 11  wherein the pH of the composition is between 5.5 and 6.5. 
     
     
         17 . The composition according to  claim 11  wherein the pH of the composition is between 5.8 and 6.5. 
     
     
         18 . The composition according to  claim 11  wherein the pH of the composition is between 5.8 and 6.2. 
     
     
         19 . The composition according to  claim 11  wherein the pH of the composition is between 6.0 and 6.2. 
     
     
         20 . The composition according to  claim 1  wherein the amount of the active ingredient is between 20-65 mg/ml.