氟胺酸-海藻糖复合物的多态转变

IF 5.2 2区 医学 Q1 PHARMACOLOGY & PHARMACY
Yuying Pang , Simon Gaisford , Oxana V. Magdysyuk , Gareth R. Williams
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引用次数: 0

摘要

将难溶性药物与小分子共形成物组合以产生无定形固体分散体(ASD),具有提高溶解速率和动力学溶解度的巨大潜力,从而提高这些活性成分的生物利用度。然而,已知这种ASD是不稳定的,并且在储存或加热时结晶。在这项工作中,我们探索了用海藻糖制备的ASD中氟非那米酸(FFA)的结晶。在一定的w/w组成比范围内制备FFA海藻糖混合物,加热至熔化并碰撞冷却以形成ASD。然后对它们进行进一步的加热/冷却循环,通过同时差示扫描量热法-X射线衍射进行监测,以观察发生的相变。这些随混合物成分的不同而变化。在短期储存后,具有低海藻糖含量(FFA:海藻糖5:1w/w)的制剂重结晶为形式I FFA,而较高海藻糖含量结晶为形式IV FFA。当加热时,所有FFA-海藻糖组合最终在熔化前重结晶为类型I。在第二次冷却循环中,具有低海藻糖含量(FFA:海藻糖5:1w/w)的体系重结晶为IV型,而较高的海藻糖含量导致FFA I型。因此,很明显,即使使用单一赋形剂,也可以通过明智地选择制剂参数来控制结晶途径。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Polymorphic transitions in flufenamic acid-trehalose composites

Polymorphic transitions in flufenamic acid-trehalose composites

The combination of poorly-soluble drugs with small molecule co-formers to generate amorphous solid dispersions (ASDs) has great potential to improve dissolution rate and kinetic solubility, and thus increase the bioavailability of these active ingredients. However, such ASDs are known to be unstable and to crystallise upon storage or heating. In this work, we explore the crystallisation of flufenamic acid (FFA) from ASDs prepared with trehalose. FFA-trehalose mixtures were prepared at a range of w/w composition ratios, heated to melting and crash cooled to form ASDs. They were then subject to a further heat/cool cycle, which was monitored by simultaneous differential scanning calorimetry – X-ray diffraction to observe the phase changes occurring. These varied with the composition of the blend. Upon short-term storage, formulations with low trehalose contents (FFA:trehalose 5:1 w/w) recrystallised into form I FFA, while higher trehalose contents crystallised to FFA form IV. When heated, all FFA trehalose combinations ultimately recrystallised into form I before melting. Upon a second cooling cycle, systems with low trehalose content (FFA:trehalose 5:1 w/w) recrystallised into form IV, while higher trehalose contents led to FFA form I. It is thus clear that even with a single excipient it is possible to control the crystallisation pathway through judicious choice of the formulation parameters.

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来源期刊
International Journal of Pharmaceutics: X
International Journal of Pharmaceutics: X Pharmacology, Toxicology and Pharmaceutics-Pharmaceutical Science
CiteScore
6.60
自引率
0.00%
发文量
32
审稿时长
24 days
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