Investigation of the impact of polymer composition and infill density of solid oral forms produced by hot-melt extrusion coupled with 3D printing on the dissolution rate of itraconazole

In recent years, scientific interest in using three-dimensional (3D) printing for drug manufacturing has
considerably increased. Modification of drug release profiles by the elaboration of complex geometries
is an application that make 3D printing and, more precisely, Fused Deposition Modeling (FDM) a
promising tool for the pharmaceutical field. In fact, nowadays, many active pharmaceutical ingredients are classified in the Biopharmaceutics Classification System class II (BCS II) since they are poorly soluble. Therefore, the aim of this work is to improve the solubility, thus, the bioavaibilty of poorly soluble drugs by the formation of an amorphous solid dispersion by the use of hot-melt extrusion (HME) coupled with FDM 3D printing.
Itraconazole (ITZ), a BCS II active molecule, was selected as the model drug. Three formulations
containing different proportions of Affinisol® 15LV (hydroxypropylmethylcellulose) and Kollidon® VA 64 (vinylpyrrolidone-vinyl acetate copolymer) and a constant proportion of 25% of ITZ were hot-melt
extruded. For each formulation, tablets with infill densities of 20%, 50% and 80% and constant weight were successfully printed (Figure 1). The results obtained with the differential scanning calorimetry (DSC) analysis show that ITZ is in an amorphous form in all the three formulations. The results of dissolution tests in 0.1 M HCl indicate that the polymer composition of the tablets has an influence on the dissolution profile of the drug. Moreover, the dissolution rate of the tablets is also influenced by their infill density.
To conclude, we have found that, for the three formulations, the lower the tablet infill is, the higher the porosity and the faster the dissolution rate are. One of the tablet formulations with an infill density of 20% even have a solubility profile similar to that of Sporanox® (the correspondent commercialized drug in Belgium) which is highly encouraging for future experiments.