Effects of crosslinking on the physical solid-state and dissolution properties of 3D-printed theophylline tablets

Abstract

Crosslinking is an established treatment to alter the physicochemical and functional properties of polymers through the creation of bonds between the polymer chains. Polymers can be crosslinked via radiation in the presence of photo-initiator. The aim of the present study was to formulate 3D-printed theophylline (THEO) tablets using polyethylene oxide (PEO) as a carrier polymer, and to study the influence of crosslinking on the drug release behavior. The tablets were 3D-printed using the aqueous solution of PEO and THEO (80:20 w/w) with a micro-extrusion-based printing setup. A photo-initiator (4-hydroxybenzophenone) was added into the printing solutions, and the injectability of the solutions was investigated prior to printing. The 3D-printed tablets were crosslinked after printing using ultraviolet (UV) or gamma-radiation, and crosslinking was verified by means of Fourier-transform infrared (FTIR) spectroscopy. The maximum injection force of aqueous printing solutions of PEO and THEO was close to that observed with the pure PEO solution. Increasing the number of printing layers in the 3D-printed tablets resulted in a slower drug release in vitro. Gamma-radiation in a nitrogen environment and UV-crosslinking made the carrier polymer (PEO) less water-soluble, but such crosslinking did not affect the release rate of the tablets. Surprisingly, even faster drug release behavior was found with the crosslinked 3D-printed tablets compared to that of non-crosslinked tablets. More research work is needed on the impact of 3D-printed tablet layering thickness and crosslinking for tailoring drug release behavior.