Abstract Nebivolol hydrochloride is an antihypertensive BCS class II drug with low solubility and high permeability prescribed as antihypertensive. Crystal engineering was applied to prepare novel cocrystal forms of nebivolol hydrochloride with general GRAS (Generally regarded as safe) molecules. Pharmaceutical cocrystals of nebivolol hydrochloride were prepared with GRAS molecules, such as 4-hydroxybenzoic acid and nicotinamide (NA), with different ratios like 1:1, 1:2, 1:3. Liquid assisted grinding and solvent evaporation method was used to prepare nebivolol hydrochloride cocrystals. All prepared crystalline forms were characterized by X-ray diffraction, differential scanning calorimetry, and FT-IR to confirm their purity and formation of cocrystals. X-ray crystal data provided details of hydrogen bonding and interactions between drug and co-formers and differential scanning calorimetry provided changes in thermal behaviour and formation of cocrystals. Physicochemical properties such as solubility and dissolution rate were measured and found that all the co-crystals dissolved faster and their equilibrium solubility is higher than the parent drug. Nebivolol hydrochloride - 4 - hydroxy benzoic acid cocrystals showed highest solubility among all crystalline forms.

中文翻译：

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具有增强溶解度的盐酸奈必洛尔药物共晶

摘要 盐酸奈必洛尔是BCS II类降压药，具有低溶解度和高渗透性，具有降压作用。应用晶体工程制备了盐酸奈必洛尔与通用GRAS（通常认为是安全的）分子的新型共晶形式。盐酸奈必洛尔的药物共晶是用GRAS分子如4-羟基苯甲酸和烟酰胺(NA)按1:1、1:2、1:3等不同比例制备的。采用液体辅助研磨和溶剂蒸发法制备盐酸奈必洛尔共晶。所有制备的晶型都通过 X 射线衍射、差示扫描量热法和 FT-IR 进行表征，以确认它们的纯度和共晶的形成。X 射线晶体数据提供了药物与共形成物之间的氢键和相互作用的详细信息，差示扫描量热法提供了热行为和共晶形成的变化。测定了溶解度和溶出度等理化性质，发现所有共晶溶解速度更快，平衡溶解度高于母体药物。奈必洛尔盐酸盐 - 4 - 羟基苯甲酸共晶在所有晶型中显示出最高的溶解度。