Polymer Templating of Supercooled Indomethacin for Polymorph Selection

被引:21
作者
McKellar, Scott C. [1 ]
Urquhart, Andrew J. [1 ]
Lamprou, Dimitrios A. [1 ]
Florence, Alastair J. [1 ]
机构
[1] Univ Strathclyde, Strathdyde Inst Pharm & Biomed Sci, Glasgow G4 0NR, Lanark, Scotland
基金
英国工程与自然科学研究理事会;
关键词
indomethacin; polymorph screening; polymer templating; polymer induced heteronucleation; glass transition; AMORPHOUS STATE; CRYSTAL; CRYSTALLIZATION; NUCLEATION; GROWTH; HETERONUCLEI; DISCOVERY;
D O I
10.1021/co200175e
中图分类号
O69 [应用化学];
学科分类号
081704 ;
摘要
Reported here-is a relatively simple technique for polymorph screening of pharmaceutical compounds that are thermally stable. Polymer libraries have previously been used as surfaces to influence, or direct, the crystalline form adopted by an active pharmaceutical ingredient on crystallization from solution. In this current work, we demonstrate the polymorph-directing effect of homopolymer surfaces in the absence of solvent by recrystallization from the supercooled melt. When the nonsteroidal anti-inflammatory drug indomethacin melted, cooled, and subsequently reheated above its glass transition temperature on an untreated surface, it has a proclivity to crystallize as its delta polymorph. ON certain polymer surfaces, however, it preferentially crystallizes as the alpha polymorph, as a direct result of polymer templating. The method is well-suited to implementation in multiwell plate formats requiring only small amounts of material and enabling multiple experiments to be carried out in parallel with samples readily characterized using X-ray powder diffraction.
引用
收藏
页码:155 / 159
页数:5
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