Long-acting implantable dosage forms containing paliperidone palmitate obtained by 3D printing.

In this work, the versatility of pressure extrusion-based printing (PEBP) was used as 3D printing process to create long-acting implantable dosage forms. Different release profiles were achieved based on the drug concentration, the way of preparation and the design of the final implants. Polycaprolactone (PCL) was used as the polymer to sustain the release of the loaded drug. Paliperidone palmitate (PP), a BCS Class II drug, used in the treatment of schizophrenia, was used as the model drug. Two PP concentrations (e.g. 5 and 10% w/w) as well as two methods of preparation before the 3D printing process, mortar and pestle and cryogenic milling, were evaluated. The amorphous state of PP was obtained by using cryogenic milling and it was maintained after printing. Two designs were printed by PEBP, a ring and a disk, to evaluate their impact on the release profile of PP. During the in vitro dissolution tests, the implant design, the amount of PP, as well as the crystalline or amorphous state of PP have shown to influence the drug release profile. During the successive steps of preparation of the long-acting implants, blends and raw materials were characterized by DSC and XRD.