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Formulation of Liquid Propofol as a Cocrystalline Solid

机译:液体异丙酚的结晶固体制剂

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摘要

This work details a crystal engineering strategy to obtain a novel solid form of the liquid drug molecule propofol using isonicotinamide as a cocrystal former. Knowledge of intermolecular hydrogen bonded supramolecular synthons has been exploited to select a potential cocrystal former based on the likely growth unit formed. The structure of the cocrystal, solved using single-crystal X-ray diffraction, is reported, confirming the molecular packing and key intermolecular interactions adopted in the novel solid form. The potential to enhance a drug’s properties is demonstrated by an increased melting point compared to the native drug form, such that the liquid drug becomes a stable solid at room temperature. Unusually, the propofol/isonicotinamide complex has three structurally similar, temperature-dependent polymorphs, and the crystal structure of each form is reported herein.
机译:这项工作详细介绍了一种晶体工程策略,该方法使用异烟酰胺作为共晶形成剂来获得液体药物分子异丙酚的新型固体形式。已经利用分子间氢键合的超分子合成子的知识来基于形成的可能的生长单元选择潜在的共晶形成剂。报告了使用单晶X射线衍射解析的共晶结构,证实了新型固体形式采用的分子堆积和关键的分子间相互作用。与天然药物形式相比,熔点的提高证明了增强药物特性的潜力,从而使液体药物在室温下变成稳定的固体。通常,丙泊酚/异烟酰胺复合物具有三个结构相似,温度依赖性的多晶型物,并且本文报道了每种形式的晶体结构。

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