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