The aim of this study was to improve the solubility and dissolution of Ibrutinib (IBR), a biopharmaceutical classification system (BCS) class II drug, by preparing binary and ternary amorphous solid dispersions (ASDs). The physicochemical properties of the ASD formulations were evaluated. Compared with crystalline IBR Form A, ASDs showed prominent improvement both in solubility and dissolution. The solubility and dissolution of IBR-HPMCAS (1:3) ASD were increased up to 9 times and 15 times than IBR Form A in the pH 6.8 buffer. Moreover, IBR-HPMCAS (1:3) ASD kept a stable amorphous state for 180 days under the accelerated stability condition (40 °C/75% RH). From Fourier Transform-Infrared spectra and ΔTg analysis, the possible hydrogen-bond interactions in IBR ASDs were pointed out to explain the improvement of solubility and stability. The results of this study demonstrated that ASD is a promising strategy to improve solubility and dissolution of poorly water soluble IBR.

本研究的目的是通过制备二元和三元无定形固体分散体 (ASD) 来提高生物制药分类系统 (BCS) II 类药物依鲁替尼 (IBR) 的溶解度和溶出度。评估了 ASD 制剂的物理化学性质。与结晶 IBR A 型相比，ASD 在溶解度和溶出度方面均表现出显着改善。IBR-HPMCAS (1:3) ASD 在 pH 6.8 缓冲液中的溶解度和溶出度比 IBR Form A 增加了 9 倍和 15 倍。此外，IBR-HPMCAS (1:3) ASD 在加速稳定性条件 (40 °C/75% RH) 下保持稳定的非晶态 180 天。从傅里叶变换红外光谱和 ΔTg 分析中，指出了 IBR ASD 中可能的氢键相互作用来解释溶解度和稳定性的提高。