Paliperidone palmitate as model of heat-sensitive drug for long-acting 3D printing application.

ABSTRACT

In this work, two technologies were used to prepare long-acting implantable dosage forms in the treatment of schizophrenia. Hot-melt extrusion (HME) as well as fused deposition modelling (FDM) were used concomitantly to create personalized 3D printed implants. Different formulations were prepared using an amorphous PLA as matrix polymer and different solid-state plasticizers. Paliperidone palmitate (PP), a heat sensitive drug prescribed in the treatment of schizophrenia was chosen as model drug. After extrusion, different formulations were characterized using DSC and XRD. Then, an in vitro dissolution test was carried out to discriminate the formulation allowing a sustained drug release of PP. The formulation showing a sustained drug release of the drug was 3D printed as an implantable dosage form. By modulating the infill, the release profile was related to the proper design of tailored dosage form and not solely to the solubility of the drug. Indeed, different release profiles were achieved over 90 days using only one formulation. In addition, a stability test was performed on the 3D printed implants for 3 months. The results showed the stability of the amorphous state of PP, independently of the temperature as well as the integrity of the matrix and the drug.