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

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.

Effect of Selected Polymers on Dissolution and Stabilization of Amorphous Form of Meloxicam

“…For the polymers used, all used polymers matched with published data [15,17,21,[23][24][25][26][27][28][29][30]. While it can be observed for that higher molecular weight chitosan (16 kDa) exhibited more spherical shape.…”

“…After that specific dilution was made to have certain concentrations and then filtered via a 45μm filter, and analyzed by UV method [14]. Drug content % and "Yield value" were calculated using the following equations [15]:…”

“…6. On the same figure, the comparison between each of the two marketed drugs (Mobic® and Moven®) and the highest release profiles of each SDs is shown while [15,17] to zero-order, Higuchi model, and korsmeyer-peppas model [18].…”

A Repurposed Drug for Brain Cancer: Enhanced Atovaquone Amorphous Solid Dispersion by Combining a Spontaneously Emulsifying Component with a Polymer Carrier

“…Amorphous solid dispersions present a promising strategy for improving the bioavailability of poorly soluble drugs [ 30 , 31 , 32 ]. Solid dispersions can be prepared by thermal methods (e.g., melting and hot-melt extrusion (HME)) [ 33 , 34 , 35 ], solvent evaporation [ 36 , 37 ], and supercritical fluid technology [ 38 , 39 , 40 ]. Binary solid dispersions of highly lipophilic drugs such as atovaquone and polymeric carriers are limited in their drug loading capacity and therefore their feasibility due to dissolution rate limitations [ 41 ].…”

Preparation and evaluation of glibenclamide binary solid dispersions prepared by fusion and solvent-fusion method

“…Several conventional and novel methods have been proposed for the preparation of SDs including, hot-melt or fusion method, solvent method, solventfusion method, supercritical anti-solvent precipitation process, electrospraying technique and etc. [15,[21][22][23][24][25]. However, very few comparisons of the in vitro performance of conventional SDs are found in literature.…”