Morphology of Porous Hosts Directs Preferred Polymorph Formation and Influences Kinetics of Solid/Solid Transitions of Confined Pharmaceuticals
Morphology of Porous Hosts Directs Preferred Polymorph Formation and Influences Kinetics of Solid/Solid Transitions of Confined Pharmaceuticals
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DOI：
10.1021/cg401170m
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发表时间：
2014-01-01
影响因子：
3.8
通讯作者：
Steinhart, Martin
中科院分区：
文献类型：
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作者：
Graubner, Gitte;Rengarajan, Gopalakrishnan Trichy;Steinhart, Martin
多孔基质的孔形态可以决定可结晶客体优先形成哪种多晶型物，并且可以影响固/固转变的动力学。阳极氧化铝（AAO，曲折度 = 1）的直圆柱形孔内的药物对乙酰氨基酚（ACE）与块状 ACE 表面膜接触时缓慢冷却，优先产生均匀取向的 II 型和/或 III 型晶体。 II 型和 III 型晶体发生的取向的特征是沿着 AAO 孔的高结构注册。 AAO孔内均匀取向的III型晶体很容易通过固/固转变转化为同样均匀取向的II型晶体。因此，我们在 AAO 中以高产率获得了均匀取向的 II 型晶体。我们认为，在 AAO 顶部的体表面薄膜中形成的体晶体的零星异质成核，加上晶体取向的动力学选择，导致正确取向的晶体沿着 100 pm 深的 AAO 孔快速生长。这种机制在具有各向同性海绵状孔（弯曲度> 1.5）且自由生长路径约为100 nm的受控多孔玻璃（CPG）中受到抑制，而其中形成了形式I。此外，CPG 中从 III 型到 II 型的转变受到抑制。可能的原因可能包括短传播路径后固/固转变的传播前沿对CPG孔壁的冲击，以及不可避免地形成由能量不利的晶界分隔的具有不同取向的II型晶粒。这里报告的结果与旨在从纳米级递送系统控制药物释放的介观晶体工程相关。纳米级容器中无法获得的多晶型物可以高产率生产。这里报告的原理可能会转移到基于纳米线的有机电子学等领域。
The pore morphology of a porous host may determine which polymorph a crystallizable guest preferentially forms and may influence the kinetics of solid/solid transitions. Slow cooling of the drug acetaminophen (ACE) inside the straight cylindrical pores of anodic aluminum oxide (AAO, tortuosity = 1) in contact with a bulk ACE surface film preferentially yields uniformly oriented form II and/or form III crystals. The occurring orientations of form II and form III crystals are characterized by high structural registry along the AAO pores. The uniformly oriented form III crystals inside the AAO pores were readily converted into likewise uniformly oriented form II crystals by a solid/solid transition. Thus, we obtained uniformly oriented form II crystals in AAO at high yields. We suggest that sporadic heterogeneous nucleation at bulk crystals formed in the bulk surface film on top of the AAO coupled with kinetic selection of crystal orientations results in fast growth of properly oriented crystals along the 100 pm deep AAO pores. This mechanism is suppressed in controlled porous glass (CPG) having isotropic spongelike pores (tortuosity > 1.5) with free growth paths on the order of 100 nm, where form I formed instead. Moreover, the transition from form III to form II is suppressed in CPG. Possible reasons may include impingement of the propagation front of the solid/solid transition on the CPG pore walls after short propagation paths and inevitable formation of form II grains with different orientations separated by energetically disadvantageous grain boundaries. The results reported here are relevant to mesoscopic crystal engineering aimed at controlled drug release from nanoscale delivery systems. Polymorphs not accessible otherwise in nanoscale containers may be produced at high yields. The principles reported here may be transferred to areas such as nanowire-based organic electronics.