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首页> 外文期刊>Crystal growth & design >Pharmaceutical Salts of Haloperidol with Some Carboxylic Acids and Artificial Sweeteners: Hydrate Formation, Polymorphism, and Physicochemical Properties
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Pharmaceutical Salts of Haloperidol with Some Carboxylic Acids and Artificial Sweeteners: Hydrate Formation, Polymorphism, and Physicochemical Properties

机译:氟哌啶醇与一些羧酸和人造甜味剂的药用盐:水合物形成,多态性和理化性质

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摘要

We report novel pharmaceutical salts of an important neuroleptic drug haloperidol (HAL) with some carboxylic acids and artificial sweeteners. The pK_a difference between HAL and the selected carboxylic acids and sweeteners suggests salt formation. All the salts were obtained from conventional solvent evaporative crystallization experiments at ambient conditions. Except formic acid, all the carboxylic acids form salt hydrates. Crystal structure analysis revealed an isostructural crystal packing in succinate, fumarate, and acetate salt hydrates. This study reports a stable polymorph of the known HAL-saccharinate, and two polymorphs of a novel salt with acesulfame. Both polymorphic sets feature significant differences in hydrogen bonding and conformations of HAL. Stability of the polymorphs was deduced by thermal analysis, comparison of the calculated density, and slurry experiments in the case of the HAL-acesulfame salt. The reported salts with artificial sweeteners could offer advantages in terms of masking the bitter taste of the parent HAL base. All the salts showed higher solubility and intrinsic dissolution rate in 10% EtOH?water medium compared to HAL. These salts provide a means of increasing the number of solid forms for HAL that facilitate selection of a suitable salt form for development of fast-dissolving HAL formulations.
机译:我们报告了一种重要的抗精神病药物氟哌啶醇(HAL)与一些羧酸和人工甜味剂的新型药物盐。 HAL与选定的羧酸和甜味剂之间的pK_a差异表明形成了盐。所有盐都是在环境条件下从常规溶剂蒸发结晶实验获得的。除甲酸外,所有羧酸均形成盐水合物。晶体结构分析表明,琥珀酸盐,富马酸盐和乙酸盐水合物中存在同构晶体堆积。这项研究报告了已知的HAL糖精的稳定多晶型物,以及与乙酰磺胺酸的新盐的两种多晶型物。两种多态集在氢键和HAL构象上均具有明显差异。在HAL-乙酰磺胺盐的情况下,通过热分析,计算密度的比较和浆液实验推导了多晶型物的稳定性。报道的与人工甜味剂形成的盐在掩盖母体HAL碱的苦味方面可能具有优势。与HAL相比,所有的盐在10%的EtOH2水介质中均显示出更高的溶解度和固有溶解率。这些盐提供了增加用于HAL的固体形式的数量的手段,其有助于选择合适的盐形式以开发快速溶解的HAL制剂。

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