The Study Of Ticagrelor Polymorphism Behaviors

Ticagrelor is a novel,selective,orally active,reversible P2Y₁₂purinoceptor antagonist.It produces a greater and more consistent inhibition of ADP-induced platelet aggregation.It is approved by the US Food and Drug Administration to improve Acute Coronary Syndrome?ACA?.Ticagrelor is a polymorphic API with the trade name of Brilinta.In this paper,the polymorphism phenomenon,thermodynamic properties,the preparation of form II and polymorphic transformation were studied,which provide basic information for drug crystallization process controlling and the preparation of formulation.1.Polymorphism phenomenon,form L and form O were obtained through polymorphism screening,form L is 2,2,2-trifluoroethanol solvate and form O is N,N-dimethylacetamide solvate,the two new forms were identified by XRPD,DSC and TGA.2.Thermodynamic properties,the solubility of Ticagrelor form I,Form II and Form III in?EtOAc+n-Heptane?binary solvents and?THF+n-Heptane?binary solvents were measured with a dynamic method at268.15 to 308.15 K.In addition,the experimental solubility data were well-correlated by using the the ideal equation,the?h equation,and modified Apelblat equation,respectively.The thermodynamic parameters including,andwere calculated.3.Crystallization process of form II was obtained successfully by optimization study.4.The solution-mediated polymorphic transformation?SMPT?was studied.UV was used to determine the concentration of the liquid phase and XRPD was used to determine the polymorphic proportion of the solid phase.FBRM was used to monitor SMPT process.The process of SMPT was explained and the mechanism was discussed.