The Screening Study Of Tolbutamide Polymorphs

In this paper, the selective crystallization of tolbutamide was studied by differentsolvents and Self-Assemble Monolayers using experimental and computationalmethods.The structures of TB I~IV forms were studied by Material Studio programmeand Hirsfield surface analysis. The effects of different solvent on selectivecrystallization of TB were discussed, and the results indicate that TB form IV can beobtained under the higher degree of supersaturation in mixed solution. While TB formI and III obtained at other conditions. Further molecular dynamic analysis confirmedthis discussion.Selective crystallization of tolbutamide on SAMs was studied throughcharacterizations of XRD and crystal morphologies. It is indicated that at lowsupersaturation (S=1.05) tolbutamide (TB) crystallized into form II on themethyl-terminated SAMs and trifluoromethyl-terminated SAMs, whereas the highestbioavailable TB crystals of form IV were obtained on phenyl-terminated SAMs,differing from the precipitated crystals from the solution including TB form I, form IIand III together.The predicted morphologies of TB I~IV polymorphs were used AE and BFDHmethods. And the binding energy values of the major faces with SAMs surface werecalculated by minimization method. These molecular modeling calculations togetherwith the experimental results illuminate the phenyl-terminated SAMs are beneficial tothe growth of TB crystals of form IV owing to the significant π-π stackings, and theCF3-SAMs are superior to TB crystals of form II owing to the hydrogen bondings,while the CH3-SAMs has a weaker advantage of TB crystals of form II owing tomolecular geometric space matching. Further time-resolved Raman spectra of TBcrystals grown on phenyl-terminated SAMs illustrate that the surface functionalgroups are paramount to adjust the heterogeneous nucleation of tolbutamidepolymorphs at low supersaturation.