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Febuxostat loaded β-cyclodextrin based nanosponge tablet: an in vitro and in vivo evaluation

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Abstract

Purpose

Febuxostat is non-purine, selective inhibitor of xanthine oxidase for treatment of gout. It exhibits poor bioavailability. The goal of the present study was to enhance the oral bioavailability of Febuxostat through β-Cyclodextrin nanosponges, subsequently reduce the dose and side effects.

Methods

Nanosponges were formed by cross-linking β-Cyclodextrin with carbonate bonds using different molar ratio (1:4, 1:6, 1:8 and 1:10 β-Cyclodextrin: crosslinker). Drug was incorporated by solvent evaporation method. Nanosponge formulations were evaluated and formulations that released (≥ 30%) at first hour followed by controlling the release (≥ 75%) at 6 h were further evaluated and tableted by direct compression. The optimum tablet formulations based upon drug release were investigated for accelerated stability testing and for comparative bioavailability with a marketed product.

Results

SEM illustrates porous and sponge like structure. DSC and FTIR studies confirmed the formation of nanosponges and encapsulation of Febuxostat within it. The zeta-potentials were high (− 21.5 to − 32.3 mV). The particle sizes were between 224.7 and 305.6 nm. The in vitro release study showed a biphasic release pattern. Oral bioavailability of selected formulation and marketed product showed enhanced Cmax (1655.0 ± 18.5 vs. 1592.7 ± 95.9 ng/mL) and AUC0−∞ (14,576.7 ± 1681.7 vs. 6449.7 ± 677.1 ng h/mL). The relative bioavailability was found to be 217.9%.

Conclusion

Nanosponges is a feasible approach to improve the oral bioavailability of Febuxostat.

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Acknowledgements

I would like to thank Dr Maha khalifa Ahmed (Lecturer of pharmaceutics department) for supporting me. I would like to give a privilege to all members of the faculty of pharmacy, Al-Azhar University for providing excellent facilities and deep support for carrying out the research work, specially (Organic Chemistry Department for help in the synthesis of nanosponges). I am thankful to EIPICO (Egypt) for generous donation of β-CD and grateful to Egyptian Petroleum Research Institute for the particle size and zeta potential work and Central Laboratory (Cairo University) for help in the DSC and FTIR work. I am thankful to Al-Roaa Laboratory for the in vivo work.

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Authors and Affiliations

  1. Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Al Azhar University, Girls Branch, Cairo, Egypt

    Omnya M. Amin, Amal Ammar & Shereen A. Eladawy

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  1. Omnya M. Amin
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  2. Amal Ammar
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  3. Shereen A. Eladawy
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Correspondence to Omnya M. Amin.

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All institutional and national guidelines for the care and use of laboratory animals were followed. Measurement of pharmacokinetic parameters of the treatments conformed to guidelines of Institutional Animal Ethical of Faculty of Pharmacy, Al-Azhar University (Approval number: 196).

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Amin, O.M., Ammar, A. & Eladawy, S.A. Febuxostat loaded β-cyclodextrin based nanosponge tablet: an in vitro and in vivo evaluation. J. Pharm. Investig. 50, 399–411 (2020). https://doi.org/10.1007/s40005-019-00464-w

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