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Co-Amorphous System (Paracetamol:Indomethacin): Investigations on Physical Stability and Intermolecular Interactions

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Pharmaceutical Chemistry Journal Aims and scope

To increase the performance of indomethacin (IND) by enhancing its water solubility and promoting its therapeutic efficiency, a ternary physically stable co-amorphous system of this poorly soluble drug with paracetamol and polyvinylpyrrolidone (PVP K30) was prepared. The effect of PVP on molecular interactions was also evaluated. Binary solid dispersions (IND:paracetamol) were prepared by a kneading method. Then, the PVP as a third component was added at different weight ratios (w/w). The generated systems were characterized by x-ray diffraction, Fourier transform infrared (FTIR) spectroscopy, scanning electronic microscopy, and 13C NMR spectroscopy. As evidenced by FTIR spectroscopy and 13C NMR investigations, the PVP interacted with paracetamol and IND through hydrogen bonds. A physical stability study under high stress conditions at relative humidity = 75% and T = 40°C for 3 months showed the ability of PVP to stabilize amorphous drug molecules. This has significantly improved the water solubility of IND at T = 37°C and pH = 7.0 in comparison with the binary solid dispersion (IND:paracetamol) or the pure state of the drug. The synergistic effect that PVP provides to the binary mixture of IND and paracetamol was the driving force behind forming a robust co-amorphous system with enhanced physical stability and water solubility.

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Acknowledgements

The authors thank Pr. Abdessalem Ben Haj Amara (Faculty of Sciences of Bizerte, Tunisia) for his considerable input and helpful discussions. The authors confirmed that this research work did not receive any specific funding.

Conflicts of Interest Statement

The authors declare that there are no conflicts of interest.

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Authors and Affiliations

  1. LMTA, l’Institut National de Recherche et d’Analyses Physico-Chimiques de Sidi-Thabet, Sidi Thabet, 2020, Tunisia

    Marouene Bejaoui, Salah Kouass & Haykel Galai

  2. RME, Faculté des Sciences de Bizerte (Université de Carthage), Jarzouna, 7021, Tunisia

    Rihem Djemi

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  1. Marouene Bejaoui
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  2. Rihem Djemi
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Correspondence to Marouene Bejaoui.

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Bejaoui, M., Djemi, R., Kouass, S. et al. Co-Amorphous System (Paracetamol:Indomethacin): Investigations on Physical Stability and Intermolecular Interactions. Pharm Chem J 57, 1330–1337 (2023). https://doi.org/10.1007/s11094-024-03042-z

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  • DOI: https://doi.org/10.1007/s11094-024-03042-z

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