Abstract Brexpiprazole (BPZ) is a typical antipsychotic drug used for the treatment of schizophrenia and depression. It is classified under BCS class-II with low aqueous solubility and high intestinal permeability. In the present investigation, we reported novel solid forms of brexpiprazole with acid coformers such as glutaric acid (GLU), fumaric acid (FUM), malonic acid (MAL) and succinic acid (SUC) via solvent drop grinding method. All the cocrystals were completely characterized by PXRD (Powder X-ray Diffraction), DSC (Differential Scanning Calorimetry) and FTIR (Fourier Transform Infrared Spectroscopy). The crystal structure is determined for malonic acid cocrystal by single-crystal X-ray diffraction method. The crystal structure revealed that the cocrystal crystallized in the triclinic crystal system with space group P-1 and the malonic acid molecules are sandwiched by brexpiprazole molecules. The solubility studies for brexpiprazole and cocrystals are established in 0.05 M acetate buffer with pH 4.3 at 25 ± 2 °C. Among all solid forms BPZ:FUM cocrystal shown 2.6 times higher solubility than parent drug whereas other cocrystals such as BPZ:GLU, BPZ:SUC and BPZ:MAL improved by 1.77, 1.59 and 1.37 times.

中文翻译：

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具有改进溶解度的新型Brexpiprazole共晶

摘要 Brexpiprazole (BPZ)是一种典型的抗精神病药物，用于治疗精神分裂症和抑郁症。它属于 BCS II 类，具有低水溶性和高肠道渗透性。在本研究中，我们通过溶剂滴磨法报道了新型固体形式的 brexpiprazole 与酸共形成物，如戊二酸 (GLU)、富马酸 (FUM)、丙二酸 (MAL) 和琥珀酸 (SUC)。所有共晶都通过 PXRD（粉末 X 射线衍射）、DSC（差示扫描量热法）和 FTIR（傅立叶变换红外光谱）进行了完全表征。通过单晶X射线衍射法确定丙二酸共晶的晶体结构。晶体结构显示共晶在空间群为P-1的三斜晶系​​中结晶，丙二酸分子被brexpiprazole分子夹在中间。brexpiprazole 和共晶的溶解度研究是在 25 ± 2 °C、pH 4.3 的 0.05 M 醋酸盐缓冲液中建立的。在所有固体形式中，BPZ:FUM 共晶的溶解度比母体药物高 2.6 倍，而其他共晶如 BPZ:GLU、BPZ:SUC 和 BPZ:MAL 分别提高了 1.77、1.59 和 1.37 倍。