Study On The Polymorph Of Linezolid

It is important for the research and development of pharmaceuticals to study the regulation of the drug polymorphs in solutions.In this article,the polymorphic linezolid,which can treat the diseases caused by garm-positive bacteria,was studied in the solution crystallization.Combining the experiments with molecular dynamics simulations methods,the effects of solvents on the regulation of the polymorphs and morphologies of linezolid were investigated.In this paper,firstly the thermodynamic properties of the dissolution process of linezolid in different solvents were studied.That provided the necessary data for the crystallization.Hirsfield surface and Material Studio were used to analyze the crystal structure and molecular conformation.By the means of cooling crystallization,the effects of solvents,supersaturation,cooling rate and crystalliztion time on the polymorphs of linezolid were studied,and the mechanism of polymorphic linezolid was revealed by the molecular dynamic simulation.Under the condition of supersaturation S=4,linezolid crystallized from methanol,ethanol and butyl acetate.Linezolid recrystallize from methanol and ethanol can obtain form II.Linezolid recrystallized from butyl acetate can obtain form III.Supersaturation,cooling rate and crystallization time don't affect the polymorphs of linezolid.Molecular dynamics simulations show that the hydrogen bond network can formed between oxazolidinone groups of two linezolid moleculars and obtain the linezolid form II.The hydrogen bonds between butyl acetate and linezolid are weak,which can induce the formation of linezolid form III.Moreover,the absorbtion energy between the solvent molecules and the crystal faces of form III is bigger than that of form II,which is helpful to the nucleation of form III.