Crystal structures and properties of two aromatic carboxylic acid-based medicinal salts of paliperidone

• Published in: Structural chemistry 2024-06, Vol.35 (3), p.967-975
• Main Authors: Shen, Zheng, Chen, Jian, Ge, Jilong, Cai, Zhuoer, Hua, Xiu-Ni, Sun, Baiwang
• Format: Article
• Language: English
• Subjects: Benzoates; Benzoic acid; Carboxylic acids; Chemistry; Chemistry and Materials Science; Computer Applications in Chemistry; Crystal structure; Crystallization; Dissolution; Hydrogen bonds; Infrared analysis; Infrared spectroscopy; Pharmacology; Physical Chemistry; Salicylic acid; Single crystals; Solubility; Theoretical and Computational Chemistry; Thermal stability; Thermodynamic properties; X ray powder diffraction; X-ray diffraction
• ISSN: 1040-0400; 1572-9001
• DOI: 10.1007/s11224-023-02247-4

Two pharmaceutical salts of paliperidone, namely, paliperidone benzoate (PLPT·BA) and paliperidone salicylate (PLPT·SA), were successfully synthesized using benzoic acid (BA) and salicylic acid (SA) as starting materials through a solvent evaporation method. Our study rectified the misidentification of PLPT·BA as a co-crystal in previous research by providing single-crystal structure data and further analysis. The salts’ structures were confirmed through ΔpKa calculations, single-crystal x-ray diffraction (SCXRD) analysis, powder x-ray diffraction (PXRD), and infrared (IR) spectroscopy, while their solubility was also evaluated. Moreover, significant enhancements in thermal stability were observed for both PLPT·BA and PLPT·SA, with increases of 39 K and 32 K, respectively, in their decomposition temperatures compared to pure PLPT. Additionally, intramolecular charge-assisted hydrogen bonds (N + –H···O) were found in both salts, which crystallized in the monoclinic system with the P 1 ¯ P-1 (2) space group. Furthermore, solubility and dissolution rate experiments indicated slight improvements in their solubility and dissolution rate compared to PLPT. This pioneering research provides crucial data on the single-crystal structures and thermal properties of PLPT·BA and PLPT·SA, laying a foundation for further investigations into their potential applications in drug formulations and pharmacology and optimizing drug formulations for enhanced clinical efficacy.