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

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 \(P\overline{1}\) 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.