This study investigated the development of high drug loading amorphous solid dispersions (ASDs) of itraconazole (ITZ) using single screw hot melt extrusion (HME) for fused deposition modelling (FDM) 3D printing (3DP). ITZ ASDs containing 20-22% w/w ITZ were prepared with Hydroxypropyl methylcellulose acetate succinate, medium grade, medium particle (HPMCAS-MMP) and processed into filaments for 3DP, while a conventional direct compression ASD was produced as a benchmark to assess the influence of manufacturing method on drug release. While both dosage forms were based on the same ASD system, the final tablet compositions differed due to the requirements of each manufacturing method. Solid-state characterisation using differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD) confirmed the amorphous nature of the formulations. Dissolution studies were conducted in phosphate buffer saline (PBS, pH 7.4). The direct compressed ASD tablets showed rapid drug release (~ 63% in 30 min) while much slower release was observed for the 3D printed tablets. At 30 min F1 (10% triethyl citrate (TEC)) released only 3% and F2 (12.5% TEC) released 6%. This behaviour may be attributed to the printed tablet's dense structure, buoyancy, and formation of a viscous hydrogel barrier at the surface. This study shows that single screw HME can be used to produce ITZ ASDs for both 3DP and conventional tabletting, while also demonstrating that the dense microstructure of 3D printed tablets limits their ability to achieve an immediate release profile. Further optimisation of formulation and tablet design, such as infill will be needed to improve release performance. These findings provide a basis for future formulation and design strategies to enhance the performance of 3D printed dosage forms.
Milliken et al. (Mon,) studied this question.