Rucaparib (Ruc) is a drug used to treat advanced ovarian cancer associated with deleterious BRCA mutations. Its commercial form, the camsylate salt (Ruc-Cam), suffers from poor aqueous solubility and thus causes low and erratic oral bioavailability. In this work, we aimed to improve the oral exposure of Ruc through cocrystallization. Liquid-assisted grinding, slurry, and solvent evaporation methods were employed to prepare new solid forms of Ruc. Cocrystals of rucaparib-theophylline monohydrate (Ruc-Thp MH), rucaparib-maltol (Ruc-Mal), and rucaparib-ethyl maltol (Ruc-Emal) were obtained. Powder X-ray diffraction, Fourier transform infrared spectroscopy, thermogravimetric analysis, differential scanning calorimetry, and dynamic vapor sorption were utilized to characterize these multi-component systems. All cocrystals dissolve faster than Ruc-Cam at pH 2.0 and 4.5, and Ruc-Thp MH displays the highest apparent solubility in pH 4.5 and 6.8 buffers. Pharmacokinetic studies in rats show that Ruc-Thp MH exhibits 2.4 times the C_max and 1.4 times the AUC_0-24h at a single dose compared with Ruc-Cam. The enhanced solubility and bioavailability of Ruc-Thp MH showcase the power of cocrystallization in addressing absorption issues in drug development.

Rucaparib (Ruc) 是一种用于治疗与有害 BRCA 突变相关的晚期卵巢癌的药物。其商业形式的甘草酸盐 (Ruc-Cam) 水溶性差，因此导致口服生物利用度低且不稳定。在这项工作中，我们旨在通过共结晶改善 Ruc 的口服暴露。采用液体辅助研磨、浆料和溶剂蒸发方法制备新的固体形式的 Ruc。获得了 rucaparib-茶碱一水合物 (Ruc-Thp MH)、rucaparib-麦芽酚 (Ruc-Mal) 和 rucaparib-乙基麦芽酚 (Ruc-Emal) 的共晶。利用粉末 X 射线衍射、傅立叶变换红外光谱、热重分析、差示扫描量热法和动态蒸汽吸附来表征这些多组分系统。在 pH 2.0 和 4.5 下，所有共晶的溶解速度都比 Ruc-Cam 快，而 Ruc-Thp MH 在 pH 4.5 和 6.8 缓冲液中表现出最高的表观溶解度。大鼠药代动力学研究表明，Ruc-Thp MH 表现出 2.4 倍的 C与 Ruc-Cam 相比，单剂量下 AUC _{0-24h的最大值}和 1.4 倍。Ruc-Thp MH 增强的溶解度和生物利用度展示了共结晶在解决药物开发中的吸收问题方面的能力。