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首页> 外文期刊>Crystal growth & design >Impact of Crystal Structure and Polymer Excipients on the Melt Crystallization Kinetics of Itraconazole Polymorphs
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Impact of Crystal Structure and Polymer Excipients on the Melt Crystallization Kinetics of Itraconazole Polymorphs

机译：晶体结构与聚合物赋形剂对伊唑康唑多晶型物的熔体结晶动力学的影响

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摘要

The crystal structure of itraconazole (ITZ) Form II has been deterinined by single-crystal X-ray diffraction, and the effects of crystal structure,and two polymer excipients, Kollidone VA64 (PVPVA64) and hydroxypropylmethyl cellulose acetate succinate (HPMCAS), on the melt crystallization kinetics of ITZ Forms I and II have been investigated. Form II structure is characterized by a unit cell similar to that of Form I, but with a different orientation of the dichlorophenyl groups. Form II displays a considerably higher crystal growth rate than Form I, which cannot be explicated by their difference in crystal density alone. Both polymers at 20% (w/w) significantly retard the crystallization of Forms I and II without altering the crystal structure of either polymorph. Crystallization kinetic analysis by the two-dimensional surface nucleation model suggests that the polymers inhibit the crystallization of ITZ from amorphous dispersions by reducing the molecular mobility in the molten state as well as augmenting the crystal-melt interfacial free energy. Form II is more sensitive than Form I to the growth inhibition by either polymer, which can be attributed to a much larger increase in the crystal-melt interfacial free energy brought about by much stronger polymer adsorption on the crystal surface of Form II.
机译：通过单晶X射线衍射进行伊唑康（ITZ）形式II的晶体结构，以及晶体结构的效果，以及两种聚合物赋形剂，kollidone Va64（PvPva64）和羟丙基甲基纤维素乙酸酯琥珀酸盐（HPMCAs）的影响。研究了ITZ形式I和II的熔体结晶动力学。形式II结构的特征在于与形式I的单位电池相似，但具有不同的二氯苯基的取向。形式II显示比形式I的晶体生长速率相当高，这不能通过它们单独的晶体密度的差异来阐述。两种聚合物在20％（w / w）显着延迟了形式I和II的结晶而不改变多晶型物的晶体结构。二维表面成核模型的结晶动力学分析表明，聚合物通过降低熔融状态中的分子迁移率以及增强晶体熔体界面自由能，抑制ITZ的结晶。形式II比通过聚合物的生长抑制更敏感，该聚合物可以归因于在形式II的晶体表面上的更强烈的聚合物吸附所带来的晶体熔体界面自由能的更大增加。

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  • 来源
    《Crystal growth & design》 |2017年第6期|共10页
  • 作者

    Zhang Shuai; Britten James F.; Chow Albert H. L.; Lee Thomas W. Y.;

  • 作者单位

    Chinese Univ Hong Kong Sch Pharm Rm 801E Shatin Hong Kong Peoples R China;

    McMaster Univ Dept Chem &

    Chem Biol Hamilton ON Canada;

    Chinese Univ Hong Kong Sch Pharm Rm 801E Shatin Hong Kong Peoples R China;

    Chinese Univ Hong Kong Sch Pharm Rm 801E Shatin Hong Kong Peoples R China;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 晶体学;
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