The effect of manufacturing method on polymer stability and drug release from PEO matrix tablets: A comparison among three methods; physical mixture, hot melt extrusion, and 3D printing

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 favourable rheological properties.  However, the thermal stability of PEOs exposed to high temperatures during FDM needs to be characterized. This research focused on the characterization of two molecular weights of PEO (7M and 0.9M) 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 oC), or by FDM 3D-printing FDM (at 220 oC). Differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), gel permeation chromatography (GPC), and dissolution tests and their kinetics studies were carried out. Results showed that thermal processes could reduce the crystallinity of PEO and induce some molecular weight reduction that varies depending on the Mw of PEO. As a result, dissolution efficiency (DE%) was influenced depending on the formulation composition and the method of manufacturing. For formulations containing PEO and HPC, 3D printed and HME tablets showed 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 molecular weight reduction in PEO.