Manipulating drug release from 3D printed dual-drug loaded polypills using challenging polymer compositions

Abstract

Combining multiple medications in a single dosage form has emerged as an important strategy for treating complex diseases and could help tackle the growing issue of polypharmacy. In this study we investigated the suitability of different dual-drug designs for achieving simultaneous, delayed and pulsatile drug release regimes using two model formulations: an immediate release erodible system of Eudragit E PO loaded with paracetamol; and an erodible swellable system of Soluplus loaded with felodipine. Both binary formulations, despite not fused deposition modelling (FDM) printable, were successfully printed using a thermal droplet-based 3D printing method, Arburg Plastic Freeforming (APF), and exhibited good reproducibility. X-ray powder diffraction (XRPD), Attenuated Total Reflectance Fourier Transform Infrared Spectroscopy (ATR-FTIR) and Differential Scanning Calorimetry (DSC) were used to assess drug-excipient interaction. The printed tablets were evaluated for drug release using in vitro dissolution testing. We found the simultaneous and delayed release designs were effective at generating the intended drug release profiles, giving insight into the types of dual-drug designs which can be used to create complex release profiles. In contrast the pulsatile tablet release was non-defined, highlighting the design limitations when using erodible materials.

Keywords: 3D printing; Arburg plastic freeforming; Controlled drug delivery; Fused deposition modelling; Polypill; Solid dispersions; Tablet design principle.