Solid pharmaceutical dosage form of ticagrelor

Abstract

The present invention relates to a solid pharmaceutical dosage form comprising ticagrelor as pharmaceutically active ingredient, to certain particles of ticagrelor and to processes of preparing the same.

1 . A solid pharmaceutical dosage form comprising particles of ticagrelor or a pharmaceutically acceptable salt or ester thereof, characterized in that at least 90% by volume of the ticagrelor particles have a particle size in the range of 1 μm to 150 μm. 
     
     
         2 . A solid pharmaceutical dosage form comprising more than 50% by weight of ticagrelor or salt or ester thereof in particle form, based on the total weight of the dosage form. 
     
     
         3 . The solid pharmaceutical dosage form according to  claim 2 , wherein at least 90% by volume of the ticagrelor particles have a particle size in the range of 1 μm to 150 μm. 
     
     
         4 . The solid pharmaceutical dosage form according to  claim 1 , further comprising at least one hydrophilic polymer and/or emulsifier. 
     
     
         5 . The solid pharmaceutical dosage form according to  claim 4 , wherein the weight ratio of ticagrelor or salt or ester thereof to the hydrophilic polymer and/or emulsifier ranges from 100:1 to 1:1. 
     
     
         6 . The solid pharmaceutical dosage form according to  claim 4 , wherein the hydrophilic polymer is selected from the group consisting of cellulose derivatives, polyvinylpyrrolidone, copolymers of polyvinylpyrrolidone, polyoxyethylenealkyl ether, polyethylenglycol, co-block-polymers of ethylenoxide and propylenoxide, polymethacrylate derivatives, polyvinylalcohol, polyvinylalcohol derivatives and polyethylenglycol derivatives. 
     
     
         7 . The solid pharmaceutical dosage form according to  claim 1 , which does not comprise any lubricant. 
     
     
         8 . The solid pharmaceutical dosage form according to  claim 1 , which further comprises an anti-thrombotic agent, in particular acetylsalicylic acid. 
     
     
         9 . A process for the preparation of a solid pharmaceutical dosage form according to  claim 1 , comprising the step of milling ticagrelor or a pharmaceutically acceptable salt or ester thereof in the presence of a polymer and/or emulsifier. 
     
     
         10 . The process according to  claim 9 , wherein the milling step is carried out as wet milling or dry milling. 
     
     
         11 . The process according to  claim 9 , wherein the polymer is a hydrophilic polymer. 
     
     
         12 . The process according to  claim 11 , wherein the hydrophilic polymer is selected from the group consisting of cellulose derivatives, polyvinylpyrrolidone, copolymers of polyvinylpyrrolidone, polyoxyethylenealkyl ether, polyethylenglycol, co-block-polymers of ethylenoxide and propylenoxide, polymethacrylate derivatives, polyvinylalcohol, polyvinylalcohol derivatives and polyethylenglycol derivatives. 
     
     
         13 . A solid composition comprising particles of ticagrelor or a pharmaceutically acceptable salt or ester thereof, wherein at least 90% by volume of the ticagrelor particles have a particle size in the range of 1 μm to 150 μm. 
     
     
         14 . The solid pharmaceutical dosage form according to  claim 4 , wherein the weight ratio of ticagrelor or salt or ester thereof to hydrophilic polymer and/or emulsifier ranges from 100:1 to 2:1. 
     
     
         15 . The solid pharmaceutical dosage form according to  claim 6 , wherein the hydrophilic polymer is a cellulose derivative selected from the group consisting of hydroxypropylmethyl cellulose, hydroxypropyl cellulose, carboxymethyl cellulose, and hydroxyethyl cellulose. 
     
     
         16 . The solid pharmaceutical dosage form according to  claim 16 , wherein the cellulose derivative is in the form of a sodium or calcium salt. 
     
     
         17 . The solid pharmaceutical dosage form according to  claim 6 , wherein the hydrophilic polymer is a copolymer of polyvinylpyrrolidone comprising vinylpyrrolidone and vinylacetate units. 
     
     
         18 . The process according to  claim 12 , wherein the hydrophilic polymer is a cellulose derivative selected from the group consisting of hydroxypropylmethyl cellulose, hydroxypropyl cellulose, carboxymethyl cellulose, and hydroxyethyl cellulose. 
     
     
         19 . The process according to  claim 12 , wherein the cellulose derivative is in the form of a sodium or calcium salt.