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

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Abstract

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.

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Acknowledgements

The authors would like to thank Yanbo times (www.yanbotimes.cn) for the support of TGA and DSC.

Funding

This work was supported by the National Nature Science Foundation of China (grant number 22201134) and the Natural Science Foundation for Colleges and Universities of Jiangsu Province (grant number 22KJB150028).

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Author notes

  1. Zheng Shen and Jian Chen contribute to the work equally.

Authors and Affiliations

  1. School of Chemistry and Chemical Engineering, Southeast University, Nanjing, 211189, China

    Zheng Shen, Jian Chen, Zhuoer Cai & Baiwang Sun

  2. School of Environmental Science, Nanjing Xiaozhuang University, Nanjing, 211171, China

    Xiu-Ni Hua

  3. Changzhou Siyao Pharmaceutical Co., Ltd, Changzhou, 213000, China

    Zheng Shen & Jilong Ge

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  1. Zheng Shen
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Contributions

Zheng Shen: Growth of crystals, draft validation and resources. Jian Chen: writing, drawing, review and editing. Jilong Ge: TGA-DSC experiments. Zhuoer Cai: single crystal analysis. Xiu-Ni Hua and Baiwang Sun: supervision.

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Correspondence to Xiu-Ni Hua or Baiwang Sun.

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Shen, Z., Chen, J., Ge, J. et al. Crystal structures and properties of two aromatic carboxylic acid-based medicinal salts of paliperidone. Struct Chem 35, 967–975 (2024). https://doi.org/10.1007/s11224-023-02247-4

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