Polymorph Selection with Morphology Control Using Solvents
详细信息 查看全文
- 作者：Manish M. Parmar ; Omar Khan ; Linda Seton ; James L. Ford
- 刊名：Crystal Growth & Design
- 出版年：2007
- 出版时间：September 2007
- 年：2007
- 卷：7
- 期：9
- 页码：1635 - 1642
- 全文大小：625K
- 年卷期：v.7,no.9(September 2007)
- ISSN：1528-7505
文摘
Sulfathiazole is a highly polymorphic model system exhibiting at least five polymorphic forms: I, II, III, IV, and V.Polymorph stability is known to be susceptible to solvent environment, and it is established that 1-propanol stabilizes the mostmetastable form I. This study examines the effect of a range of alcohols on polymorph selection and attempts to elucidate themechanism. The role of the alcohol functional group in the polymorph selection process is thus investigated and evaluated. Crystalswere characterized using optical microscopy, SEM, PXRD, DSC, IR, and single-crystal X-ray diffraction for their polymorphicidentity. The role of solvent in the stabilization of polymorphs was investigated by visualizing and calculating energy requirementsfor the interaction of each solvent molecule with 
fchars/alpha.gif" BORDER=0>- and fchars/beta2.gif" BORDER=0 ALIGN="middle">-dimers of sulfathiazole, using Cerius2 modeling software. This studyshowed that solvent had a significant impact on polymorph selection. In common with 1-propanol, 1-butanol was found to stabilizeform I by inhibiting the formation of the fchars/beta2.gif" BORDER=0 ALIGN="middle">-dimer, which is necessary for nucleation of and transformation to forms II-IV. Shorterchain alcohols and branched chain alcohols such as methanol, 2-propanol, and ethanol did not stabilize form I but stabilized formsII, III, and IV, respectively, showing that it is not only the alcohol functionality but also the steric effects of the alkyl chain thatcontributed to the effect. Sulfathiazole form I normally has a needlelike morphology. Form I with a modified rodlike morphologywas produced by crystallization from 1-propanol with the addition of methanol in low concentration, showing that it is possible tocontrol the morphology and selectively isolate polymorphs.
fchars/alpha.gif" BORDER=0>- and fchars/beta2.gif" BORDER=0 ALIGN="middle">-dimers of sulfathiazole, using Cerius2 modeling software. This studyshowed that solvent had a significant impact on polymorph selection. In common with 1-propanol, 1-butanol was found to stabilizeform I by inhibiting the formation of the fchars/beta2.gif" BORDER=0 ALIGN="middle">-dimer, which is necessary for nucleation of and transformation to forms II-IV. Shorterchain alcohols and branched chain alcohols such as methanol, 2-propanol, and ethanol did not stabilize form I but stabilized formsII, III, and IV, respectively, showing that it is not only the alcohol functionality but also the steric effects of the alkyl chain thatcontributed to the effect. Sulfathiazole form I normally has a needlelike morphology. Form I with a modified rodlike morphologywas produced by crystallization from 1-propanol with the addition of methanol in low concentration, showing that it is possible tocontrol the morphology and selectively isolate polymorphs.