3D printed extended release tablets for once daily use: An in vitro and in vivo evaluation study for a personalized solid dosage form

Abstract

Fused deposition modeling (FDM)-3D printing enables the manufacturing of dosage forms with personalized doses and controllable release profiles. Parkinson's disease is a neurodegenerative disorder that causes motor complications. In the treatment of the disease, the nonergot dopamine receptor agonist pramipexole is used in gradually increasing doses depending on patient's needs. Hence, there are various dosed commercial products of pramipexole and it is a suitable model drug for the preparation of personalized-dose 3D printed dosage forms. In this study, we prepared extended release 3D tablets of pramipexole for once daily use in Parkinson's disease. Herein, 12 different 3D tablet formulations were prepared and in vitro characterizations were performed on these formulations. The formulations were compared with the marketed tablet and the optimum formulation was selected. The chosen formulation was prepared with commercially available doses of pramipexole and also with intermediate doses which are not available in the market to demonstrate the applicability of 3D printing in personalized dosing. Stability studies, which have innovative features for 3D tablets, were conducted in optimum 3D tablet formulation for 6 months at 25 °C/60% relative humidity (RH) and 40 °C/75% RH conditions. After oral administration of the optimum 3D tablets and the marketed tablets (in the same dose) to the rats, 24-hour plasma profiles were obtained and pharmacokinetic parameters were calculated. 3D tablets were successfully prepared in personalized doses and their properties were similar for almost all doses. The optimum 3D tablet formulation was found to be stable during the stability tests. 3D tablet and marketed tablet performed similar plasma profiles. The relative bioavailability of 3D tablet formulation was calculated as 107.6% compared with the marketed tablet. Briefly, in vitro and in vivo evaluations demonstrated that FDM-3D printing is a promising technology for the development of personalized dosage forms with extended release property and comparable to conventional ones.

Keywords: 3D printing; Extended release; Hot melt extrusion; Personalized dosing; Pharmacokinetic; Pramipexole.