Development of pH-Responsive Polypills via Semi-Solid Extrusion 3D Printing

Abstract

The low bioavailability of orally administered drugs as a result of the instability in the gastrointestinal tract environment creates significant challenges to developing site-targeted drug delivery systems. This study proposes a novel hydrogel drug carrier using pH-responsive materials assisted with semi-solid extrusion 3D printing technology, enabling site-targeted drug release and customisation of temporal release profiles. The effects of material parameters on the pH-responsive behaviours of printed tablets were analysed thoroughly by investigating the swelling properties under both artificial gastric and intestinal fluids. It has been shown that high swelling rates at either acidic or alkaline conditions can be achieved by adjusting the mass ratio between sodium alginate and carboxymethyl chitosan, enabling site-targeted release. The drug release experiments reveal that gastric drug release can be achieved with a mass ratio of 1:3, whilst a ratio of 3:1 allows for intestinal release. Furthermore, controlled release is realised by tuning the infill density of the printing process. The method proposed in this study can not only significantly improve the bioavailability of oral drugs, but also offer the potential that each component of a compound drug tablet can be released in a controlled manner at a target location.