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Development of ketoprofen-p-aminobenzoic acid co-crystal: formulation, characterization, optimization, and evaluation

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Abstract

In the present study, ketoprofen-p-aminobenzoic acid (KP-PABA) co-crystal was prepared, to advance solubility and dissolution rate of drug, by solvent evaporation technique employing central composite experimental design. The optimized batch as recommended by the experimental design was characterized by FTIR, DSC, XRD, SEM, and NMR studies and further, evaluated for in-vitro and in-vivo anti-inflammatory and analgesic activities. The solubility and % drug release of different batches of co-crystal was found to be between 34.20–60.11 µg/ml and 68.11–93.45%, respectively. Physical characterization by X-ray diffraction spectra and differential scanning calorimetric studies confirmed the crystallinity of prepared co-crystal. The IC50 value of optimized batch of co-crystal formulation and pure drug was observed as 248.79 µg/ml and 524.40 µg/ml, respectively, displaying that co-crystal formulation possesses more percentage protection against protein denaturation than the drug ketoprofen. The results of in-vivo anti-inflammatory activity carried out by rat paw edema method revealed that the optimized batch of co-crystal preparation provided a significant % inhibition in paw volume in contrast to standard drug in wistar rats. Hence, the crystalline molecular complex of ketoprofen with p-aminobenzoic acid was documented that set out an improvement in solubility and also in anti-inflammatory activity of the drug in wistar rats.

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Acknowledgements

The authors are highly grateful to Department of Pharmaceutical Sciences, Central Instrumentation Laboratory and Material Science Laboratory, Guru Jambheshwar University of Science and Technology, Hisar for providing necessary facilities to carry out the research.

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  1. Departmental of Pharmaceutical Sciences, Guru Jambheshwar University of Science and Technology, Hisar, 125001, India

    Meenakshi Bhatia, Ashwani Kumar & Sunita Devi

  2. Departmental of Chemistry, Guru Jambheshwar University of Science and Technology, Hisar, 125001, India

    Vikas Verma

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  1. Meenakshi Bhatia
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Correspondence to Sunita Devi.

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The procedure followed for animal handling is in accordance with the protocol as approved for animal study (CPCSEA Reg. no-IAEC/2020/10-18) by the Institutional Animal Ethical Committee, Guru Jambheshwar University of Science and Technology, Hisar, India.

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Bhatia, M., Kumar, A., Verma, V. et al. Development of ketoprofen-p-aminobenzoic acid co-crystal: formulation, characterization, optimization, and evaluation. Med Chem Res 30, 2090–2102 (2021). https://doi.org/10.1007/s00044-021-02794-7

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