Orally Disintegrating Tablets Containing Melt Extruded Amorphous Solid Dispersion of Tacrolimus for Dissolution...

Area of Science:

• Pharmaceutical Technology
• Materials Science
• Drug Delivery

Background:

• Tacrolimus (TAC) exhibits poor aqueous solubility and dissolution, limiting its therapeutic efficacy.
• Developing stable amorphous solid dispersions is crucial for improving the bioavailability of poorly soluble drugs like TAC.

Purpose of the Study:

• To prepare and characterize amorphous solid dispersions of Tacrolimus (TAC) using hot melt extrusion.
• To evaluate the stability and dissolution enhancement of TAC amorphous solid dispersions.
• To assess the suitability of hot melt extrusion for producing stable TAC solid dispersions for oral delivery.

Main Methods:

• Hot melt extrusion with Polyvinylpyrrolidone vinyl acetate (PVP VA64), Soluplus®, and Hydroxypropyl Cellulose (HPC).
• Molecular modeling using Hansen Solubility Parameters for miscibility assessment.
• Powder X-ray diffraction (PXRD), Differential Scanning Calorimetry (DSC), and Fourier Transform Infrared (FTIR) spectroscopy for characterization.
• Stability studies under accelerated conditions and dissolution testing.

Main Results:

• Hot melt extrusion yielded stable amorphous solid dispersions of TAC with PVP VA64, Soluplus®, and HPC.
• Characterization confirmed the conversion of crystalline TAC to amorphous form, stabilized by hydrogen bonding.
• The amorphous solid dispersions showed significantly enhanced dissolution rates, releasing >80% TAC in 15 min.
• Extrudates remained stable for 3 months under accelerated conditions without recrystallization.

Conclusions:

• Hot melt extrusion is an effective method for producing stable amorphous solid dispersions of Tacrolimus.
• These solid dispersions markedly improve TAC solubility and dissolution, offering advantages for oral dosage forms.
• The developed solid dispersions retained their enhanced properties when formulated into orally-disintegrating tablets.