The effect of manufacturing method; direct compression, hot-melt extrusion, and 3D printing on polymer stability and drug release from polyethylene oxide tablets

Thermal 3D printing has gained substantial attention in pharmaceutical formulation, especially concerning its potential use in personalized dose delivery. The choice of a printable polymer is crucial in this technique, but it is restricted due to technical issues such as thermal stability and thermal-rheological properties of the polymers. Polyethylene oxide (PEO) is a widely used polymer in drug formulation designs, with potential application in 3D printing due to its favorable rheological properties. However, the thermal stability of PEOs exposed to high temperatures during fused deposition modeling (FDM) needs to be characterized. This research focused on the characterization of two molecular weights (Mw) of PEO (7 and 0.9 M) under various manufacturing methods and formulation compositions. PEO was mixed with other low-viscosity polymers of hydroxypropyl cellulose (HPC) or ethyl cellulose (EC) to achieve printable formulations (PEO/HPC or PEO/EC). Tablets were manufactured by direct compression, compression of hot-melt extrudates (HME) at 150°, or by FDM 3D-printing at 220°. Differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), gel permeation chromatography (GPC), dissolution tests, and their kinetics studies were carried out. Results demonstrated that thermal processes could reduce the crystallinity of PEO and induce Mw reduction that varies depending on the Mw of PEO. As a result, dissolution efficiency (DE%) varied based on the formulation composition and manufacturing method. For formulations containing PEO and HPC, 3D-printed and HME tablets exhibited higher DE (>60%) compared to directly compressed tablets (DE < 50%), while for those with PEO and EC, 3D printing reduced DE% to <26% compared to direct compression (~30%) and HME tablets (~50%). This was attributed to the hydrophobic nature of EC and the increased hardness of the printed tablets, preventing tablet disintegration during dissolution, which outweighs the Mw reduction in PEO.