How do infill density and polymer composition of tablets produced by hotmelt extrusion coupled with Fused Deposition Modeling 3D printing influence the dissolution profile of a BCS II molecule ?

Introduction: During last years, the use of three-dimensional (3D) printing for drug manufacturing has
considerably increased in the field of pharmaceutical research. The development of complex geometries leading to different drug release profiles is an application that make 3D printing and, more specifically, Fused Deposition Modeling (FDM) a promising tool. In fact, many active pharmaceutical ingredients are classified in the Biopharmaceutics Classification System class II (BCS II) since they are poorly soluble.
Thus, the goal of this work is to enhance the solubility and the bioavaibilty of poorly soluble drugs by the use of hot-melt extrusion (HME) coupled with FDM to form of an amorphous solid dispersion.
Method: The selected model drug was Itraconazole (ITZ), a BCS II active molecule. Hot-melt extrusion process was performed on three formulations containing 25% of ITZ and different proportions of Affinisol® 15LV (hydroxypropylmethylcellulose) and Kollidon® VA 64 (vinylpyrrolidone-vinyl acetate copolymer). For each formulation, tablets with infill densities of 20%, 50% and 80% were printed (Figure 1).
Results: Differential scanning calorimetry (DSC) analysis shows that the three formulations contain ITZ in its amorphous form. The results of dissolution tests in 0.1 M HCl indicate that the dissolution profile of the drug is influenced by the polymer composition and the infill density of the tablets.
Conclusions: In conclusion, for the three formulations, the lower the tablet infill is, the higher the porosity and the faster the dissolution rate are. A solubility profile similar to that of Sporanox® (the correspondent commercialized drug in Belgium) is even obtained with one of the tablet formulations with an infill density of 20%, which is highly encouraging for future experiments.