Norfloxacin co-amorphous salt systems: Effects of molecular descriptors on the formation and physical stability of co-amorphous systems

作者：Deng, Yuehua; Deng, Wenhao; Huang, Wenquan; Zheng, Zhiyong; Zhang, Rui; Liu, Shiyuan^*; Jiang, Yanbin^*

来源：Chemical Engineering Sciences, 2022, 253: 117549.

DOI：10.1016/j.ces.2022.117549

• Co-amorphous
• Norfloxacin
• Hansen solubility parameters
• Multivariate data analysis
• Molecular descriptors

Amorphization technology has been a promising strategy to improve the solubility and dissolution of drugs. This study aims to prepare norfloxacin (NFX) co-amorphous (CA) systems and evaluate the association between molecular descriptors and the formation and physical stability of NFX CAs. The molecular miscibility between NFX and 17 co-former candidates was firstly predicted using Hansen solubility parameters (HSPs) and six NFX CAs were successfully prepared by dry ball mill. Compared with crystalline NFX, four NFX CAs showed enhanced solubility (up to 2.50-fold) and dissolution rates. NFX CAs exhibited excellent physical stability under dry conditions. According to the quantitative calculations of Pearson correlation coefficient and Ridge regression, molecular decriptors have a great effect on NFX CA formation with structural parameters (Weight, VDW_vol, VDW_area, Rings) stronger than misci bility parameter Delta delta and pKa. These molecular descriptors corresponding to pi center dot center dot center dot pi interactions, molecul a rmiscibility and ionic interactions are also responsible for physical stability. The results demonstrate that NFX CA can be stably formed if the co-former has more rings, smaller Delta delta (less than or close to 5 MPa0.5)and larger Delta pKa. This study offers a potential strategy to screen and design a CA system using multivari-ate data analysis based on theoretical considerations of molecular descriptors.