Melt crystallization of metacetamol polymorphs using vertical Bridgman method

IF 2.5 4区材料科学 Q3 CRYSTALLOGRAPHY

Journal of Crystal Growth Pub Date : 2026-02-01 Epub Date: 2025-11-22 DOI:10.1016/j.jcrysgro.2025.128428

Architha Natarajan, Srinivasan Karuppannan

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引用次数: 0

Abstract

The crystallization behavior of metacetamol polymorphs from the melt was systematically investigated using a custom-designed Vertical Bridgman (VB) furnace. By varying the ampoule translation rate between 1.5 and 24 cm/min, corresponding to cooling rates of approximately 3.6 to 58.5 °C/min, distinct polymorphic outcomes were observed. Form I emerged predominantly at both low (3.6–7.2 °C/min) and high (13.5–58.5 °C/min) cooling rates, whereas the metastable form II was confined to a narrow intermediate cooling-rate window (7.3–13.4 °C/min). These findings underscore the critical influence of cooling rate on polymorph selection during melt crystallization. Powder X-ray diffraction (PXRD) confirmed the crystal systems and enabled refinement of lattice parameters, while differential scanning calorimetry (DSC) and thermogravimetric-differential thermal analysis (TG-DTA) provided insights into the thermal properties of the polymorphs. This work demonstrates a scalable, solvent-free approach to selectively obtain metacetamol polymorphs, offering valuable implications for controlled pharmaceutical manufacturing.

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垂直Bridgman法熔体结晶对乙酰氨基酚多晶的影响

采用自行设计的立式Bridgman （VB）炉，系统地研究了熔体中metacetamol多晶的结晶行为。通过改变安瓿转换速率在1.5和24 cm/min之间，对应于大约3.6到58.5°C/min的冷却速率，观察到不同的多晶化结果。形式I主要在低（3.6-7.2°C/min）和高（13.5-58.5°C/min）冷却速率下出现，而亚稳形式II仅限于狭窄的中间冷却速率窗口（7.3-13.4°C/min）。这些发现强调了冷却速率对熔体结晶过程中多晶选择的关键影响。粉末x射线衍射（PXRD）证实了晶体系统，并使晶格参数得以细化，而差示扫描量热法（DSC）和热重-差热分析（TG-DTA）提供了对多晶物热性质的深入了解。这项工作展示了一种可扩展的，无溶剂的方法来选择性地获得甲基乙酰氨基酚多态性，为控制药物制造提供了有价值的意义。

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来源期刊

Journal of Crystal Growth 化学-晶体学

CiteScore

3.60

自引率

11.10%

发文量

373

审稿时长

65 days

期刊介绍： The journal offers a common reference and publication source for workers engaged in research on the experimental and theoretical aspects of crystal growth and its applications, e.g. in devices. Experimental and theoretical contributions are published in the following fields: theory of nucleation and growth, molecular kinetics and transport phenomena, crystallization in viscous media such as polymers and glasses; crystal growth of metals, minerals, semiconductors, superconductors, magnetics, inorganic, organic and biological substances in bulk or as thin films; molecular beam epitaxy, chemical vapor deposition, growth of III-V and II-VI and other semiconductors; characterization of single crystals by physical and chemical methods; apparatus, instrumentation and techniques for crystal growth, and purification methods; multilayer heterostructures and their characterisation with an emphasis on crystal growth and epitaxial aspects of electronic materials. A special feature of the journal is the periodic inclusion of proceedings of symposia and conferences on relevant aspects of crystal growth.