Search

Many active principles belong to the second class of the Biopharmaceutics Classification System due to their low aqueous solubility. Elaboration of new solid oral forms by hot-melt extrusion and fused deposition modeling appears as a promising tool to increase the dissolution rate of these drugs. Indeed, hot-melt extrusion allows the amorphisation of drugs and forms with complex geometries are built by 3D printing. Therefore, the goal of this work is to enhance the dissolution rate of poorly soluble drugs using hot-melt extrusion coupled with fused deposition modeling. Four formulations containing Affinisol® 15LV, Kollidon® VA64 and a challenging amount of itraconazole (25 % (wt.)) were successfully printed into forms of 20, 50 and 80 % infill densities. Differential scanning calorimetry analysis has shown that itraconazole remained amorphous during 52 weeks. The drug release rate was highly improved compared to itraconazole in a crystalline form. The dissolution rate was influenced by the infill density and the polymer composition of printed forms which could modify respectively the surface to volume ratio and the distribution of the components in the printed forms. One formulation printed with 20 % infill density even had a solubility profile similar to that of Sporanox®, the commercialized drug product in Belgium.

In recent years, fused deposition modeling has become one of the most used three-dimensional printing technologies in the pharmaceutical field. The production of personalized dosage forms for individualized therapy and the modification of the drug release profile by the elaboration of complex geometries make fused deposition modeling a promising tool for small-scale production. However, fused deposition modeling has a considerable number of challenges to overcome. They are divided into three categories of parameters. Material-specific parameters encompass the physicochemical properties of the filament, like thermal, mechanical and rheological properties. They determine the feasibility of the printing process. Operation-specific parameters relate to the processing conditions of printing, such as printing temperature and infill density, which have an influence on the final quality and on the dissolution behavior of the objects. The printer equipment is defined by the machine-specific parameters. Some modifications of this equipment also enhance the performance of the printing process. The aim of this review is to highlight the major fused deposition modeling critical process parameters in the pharmaceutical field and possible solutions in order to speed up the development of objects in the pharmaceutical market.