Novel composition for treatment of essential thrombocythemia

Abstract

The present invention relates to a novel pharmaceutical composition free of gastric coating comprising anagrelide hydrochloride in combination with a non-pH dependent polymer and a pharmaceutically acceptable watersoluble acid and its use for the treatment of essential thrombocythemia.

1 . A pharmaceutical composition free of gastric coating comprising anagrelide HCl, a non-pH dependent polymer and a pharmaceutically acceptable water soluble acid, wherein the non-pH dependent polymer is selected from the group consisting of a polyacrylacid, a cellulose derivative, and a polyacrylamide, and wherein the amount of the non-pH dependent polymer is between 1.5 and 2.5 fold of the anagrelide (w/w). 
     
     
         2 . A pharmaceutical composition according to  claim 1 , wherein the anagrelide HCl is in the form of particles, and wherein at least 90% of said particles are smaller than 10 μm in diameter. 
     
     
         3 . A pharmaceutical composition according to  claim 1 , wherein the anagrelide HCl is present in an amount of between 0.5 mg and 5 mg. 
     
     
         4 . A pharmaceutical composition according to  claim 1 , wherein the amount of the non pH dependent polymer is about 1.5 fold to 2.5 fold greater than the amount of the pharmaceutically active agent (w/w). 
     
     
         5 . A pharmaceutical composition according to  claim 1 , wherein the non-pH dependent polymer is a polyacrylacid and is present in an amount of between 1 mg and 10 mg. 
     
     
         6 . A pharmaceutical composition according to  claim 1 , wherein the pharmaceutically acceptable water soluble acid is selected from the group consisting of adipic acid, ascorbic acid, citric acid, fumaric acid, malic acid, succinic acid, tartaric acid and a mixture thereof. 
     
     
         7 . A pharmaceutical composition according to  claim 1 , wherein the water soluble acid is present in an amount of between 5 mg and 40 mg. 
     
     
         8 . A pharmaceutical composition according to  claim 1 , wherein the anagrelide HCl has a mean particle size of about 5 μm. 
     
     
         9 . A pharmaceutical composition according to  claim 1 , further comprising microcrystalline cellulose. 
     
     
         10 . A pharmaceutical composition according to  claim 1 , wherein the microcrystalline cellulose is present in an amount of between 10 mg and 150 mg. 
     
     
         11 . A pharmaceutical composition according to  claim 1  having an in-vitro release rate of at least 45% within 8 hours. 
     
     
         12 . A pharmaceutical composition according to  claim 1 , comprising anagrelide HCl, a polyacrylacid, citric acid, microcrystalline cellulose and magnesium stearate. 
     
     
         13 . A pharmaceutical composition according to  claim 1 , wherein the pharmaceutical composition is in the form of a tablet. 
     
     
         14 . A pharmaceutical composition according to  claim 3 , wherein the composition comprises anagrelide HCl in an amount of between 2 mg and 3 mg. 
     
     
         15 . A pharmaceutical composition according to  claim 1 , wherein the non-pH dependent polymer is a carbomer. 
     
     
         16 . A pharmaceutical composition according to  claim 5 , wherein the polyacrylacid is present in an amount of between 3 and 4 mg. 
     
     
         17 . A pharmaceutical composition according to  claim 7 , wherein the water soluble acid is present in an amount of between 15 mg and 19 mg. 
     
     
         18 . A pharmaceutical composition according to  claim 10 , wherein the microcrystalline cellulose is present in an amount of between 70 mg and 80 mg. 
     
     
         19 . A method of treating essential thrombocythemia, comprising administering to a patient in need thereof a pharmaceutical composition free of any gastric coating, the composition comprising anagrelide HCl, a non-pH dependent polymer, and a pharmaceutically acceptable water soluble acid, wherein the non-pH dependent polymer is selected from the group consisting of a polyacrylacid, a cellulose derivative, and a polyacrylamide, and wherein the amount of the non-pH dependent polymer is between 1.5 and 2.5 fold of the anagrelide (w/w).