Study On The Polymorphic Behavior Of Prasugrel Hydrogen Sulfate

Polymorphs of solid drugs,because of their different crystal structure,lead to differences in their physical and chemical properties,and affect the drug solubility,dissolution rate of different,resulting in polymorphic drug bioavailability and clinical efficacy of the difference.Grasping the mechanism of polymorphic nucleation,controlling the crystal transformation conditions,determining the impact of polymorphic factors,can not only for the polycrystalline screening to provide theoretical support,but also on the polymorphic drug product processing optimization is of great significance.The in-depth study and discussion about polymorphs screening and transformation process of polymorph were carried out in this paper,and Prasugrel hydrogen sulfate was chosen as the research subject.Prasugrel hydrogen sulfate is a platelet inhibitor and chosen in this paper since it has five polymorphs and one amorphous.Two novel Prasugrel hydrogen sulfates were found in the polymorphic screening experiments,and two amorphous products.And used a systematic method combing DSC,TG,PXRD,FT-IR and moisture analyses to characterize and study the stability of the polymorphs.The solubility of Prasugrel hydrogen sulfate polymorphs was determined by the gravimetric method,the solubility data were correlated by Apelblat equation,the enthalpy of dissolution and the entropy of dissolution of Form ? and Form ? were calculated based on regression of the solubility data with utilizing Van't-Hoff equation.Powder X-ray diffraction was used in the quantitative analysis of Prasugrel hydrogen sulfate,and the calibration models formed from binary mixtures of Form ? and Form ? were built to quantify the amount of two forms in powder mixture.Solvent-mediated crystallization of Prasugrel hydrogen sulfate FormI to Form ? was monitored offline by X-ray diffraction,the rate determining step during this process was determined by a gravimetrical method.It was found that the solvent had an effect on the formation of Prasugrel hydrogen sulfate polymorphism by the polymorphic screening.The effect of the solvent on the thermodynamics of crystallization was discussed from the perspectives of the hydrogen bond donor capacity and the acceptability of the solvent.