The crystallization of poorly soluble drug molecules with an excipient into new solid phases called cocrystals has gained a considerable popularity in the pharmaceutical field. In this work, the cocrystal approach was explored for a very poorly water soluble antifungal active, itraconazole (ITR), which was, for the first time, successfully converted into this multicomponent solid using an aromatic coformer, terephthalic acid (TER). The new cocrystal was characterized in terms of its solid-state and structural properties, and a panel of pharmaceutical tests including wettability and dissolution were performed. Evidence of the cocrystal formation was obtained from liquid-assisted grinding, but not neat grinding. An efficient method of the ITR–TER cocrystal formation was ball milling. The stoichiometry of the ITR–TER phase was 2:1 and the structure was stabilized by H-bonds. When comparing ITR–TER with other cocrystals, the intrinsic dissolution rates and powder dissolution profiles correlated with the aqueous solubility of the coformers. The rank order of the dissolution rates of the active pharmaceutical ingredient (API) from the cocrystals was ITR–oxalic acid > ITR–succinic acid > ITR–TER. Additionally, the ITR–TER cocrystal was stable in aqueous conditions and did not transform to the parent drug. In summary, this work presents another cocrystal of ITR that might be of use in pharmaceutical formulations.

中文翻译：

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新型伊曲康唑对苯二甲酸共晶体的鉴定和药物表征。

难溶性药物分子与赋形剂的结晶成为新的称为共晶体的固相，在制药领域已广受欢迎。在这项工作中，探索了共晶方法用于水溶性极差的抗真菌活性物质伊曲康唑（ITR），该化合物首次使用芳族共成型物对苯二甲酸（TER）成功地转化为这种多组分固体。新的共晶体以其固态和结构性质为特征，并进行了包括润湿性和溶解性在内的一系列药物测试。共晶形成的证据是通过液体辅助研磨而不是纯研磨获得的。ITR-TER共晶形成的有效方法是球磨。ITR-TER相的化学计量比为2：如图1所示，通过H键使结构稳定。当将ITR-TER与其他共结晶进行比较时，固有溶解速率和粉末溶解曲线与共形成剂的水溶性相关。共结晶中活性药物成分（API）溶出度的等级顺序为ITR-草酸> ITR-琥珀酸> ITR-TER。另外，ITR-TER共晶在水性条件下稳定，并且不会转化为母体药物。总之，这项工作提出了ITR的另一种共晶，可能在药物制剂中使用。共结晶中活性药物成分（API）溶出度的等级顺序为ITR-草酸> ITR-琥珀酸> ITR-TER。此外，ITR-TER共晶在水性条件下稳定，并且不会转化为母体药物。总之，这项工作提出了ITR的另一种共晶，可能在药物制剂中使用。共晶体中活性药物成分（API）溶出度的等级顺序为ITR-草酸> ITR-琥珀酸> ITR-TER。另外，ITR-TER共晶在水性条件下稳定，并且不会转化为母体药物。总而言之，这项工作提出了ITR的另一种共晶，可用于药物制剂。