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Using Supercritical Fluid Technology (SFT) in Preparation of Tacrolimus Solid Dispersions

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Abstract

Tacrolimus is an immunosuppressant agent that suffers from poor and variable bioavailability. This can be related to limited solubility and dissolution. The main objective of this study is to use SFT to prepare solid dispersions of tacrolimus in order to enhance its dissolution. SFT was selected since it offers several advantages over conventional techniques such as efficiency and stability. Several solid dispersions of tacrolimus were prepared using SFT to enhance its dissolution. The selected polymers included soluplus, PVP, HPMC, and porous chitosan. TPGS was used as a surfactant additive with chitosan, HPMC, and PVP. Soluplus dispersions were used to study the effect of processing parameters (time, temperature, and pressure) on loading efficiency (LE) and dissolution of the preparation. Physicochemical characterization was performed using DSC, X-ray diffraction, FTIR analysis, SEM, and in vitro drug release. Stability testing was evaluated after 3 months for selected dispersions. Significant improvement for the release profile was achieved for the prepared dispersions. Better release achieved in the soluplus dispersions which reached maximum cumulative release equal to 98.76% after 24 h. Drug precipitated in its amorphous form in all prepared dispersions except those prepared from chitosan. All dispersions were physically stable except for PVP preparations that contained TPGS which started to re-crystallize after one month. Prepared dispersions were proved to be affected by supercritical processing parameters. In conclusion, SFT was successfully used to prepare dispersions of tacrolimus that exhibited higher dissolution than raw drug. Dissolution rate and stability are affected by the type of the polymer.

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Acknowledgments

This work was supported by the Jordan University of Science and Technology (Grant number 140/2013).

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Authors and Affiliations

  1. Department of Pharmaceutical Technology, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, Jordan

    Rana M. Obaidat, Bassam M. Tashtoush & Alaa Abu Awad

  2. Pharmaceutical Research Unit, Amman, Jordan

    Rana T. Al Bustami

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  1. Rana M. Obaidat
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  2. Bassam M. Tashtoush
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  3. Alaa Abu Awad
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Obaidat, R.M., Tashtoush, B.M., Awad, A.A. et al. Using Supercritical Fluid Technology (SFT) in Preparation of Tacrolimus Solid Dispersions. AAPS PharmSciTech 18, 481–493 (2017). https://doi.org/10.1208/s12249-016-0492-4

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