Additive manufacturing of polymer-based drug delivery systems: Effects of semi-solid ink composition and manufacturing process parameters on structural and drug release properties

Abstract

Controlled release drug delivery systems enable the maintenance of drug levels within the therapeutic window for extended periods, thereby enhancing the treatment efficacy and patient compliance. However, there is a growing desire for further customization of drug products to meet the individual needs of patients. Various 3D printing techniques have emerged as potential manufacturing options that enable the personalization of the product size, shape, dosage, and drug release kinetics. In particular, the semi-solid extrusion (SSE) method has shown promise due to its versatility and compatibility with a wide range of materials and drugs. However, the process applies specific rheological requirements on the materials used, and optimization of the printing process is necessary for new formulations.

This thesis investigates the potential of SSE in the preparation of polymer-based drug delivery systems for the long-term macromolecule release. Extrudable inks containing biodegradable polymeric microspheres within a Carbopol hydrogel matrix were formulated, and their rheological properties and printability were assessed. Additionally, a solvent-based post-processing method was developed for tailoring the microstructure of the printed objects. Finally, microspheres encapsulating the model hydrophilic macromolecule drug fluorescein isothiocyanate-dextran (FITC-dextran) were formulated and incorporated into the inks, and drug release from the printed systems was studied in vitro. The results indicated that the microsphere concentration within the ink influenced its rheological properties and printability. Notably, the extrudate swell phenomenon was identified as a critical factor in the printing process, affecting both the final object resolution and suitable process parameters. Post-processing by exposure to solvent vapor caused progressive fusing of the particles, increasing the object density and mechanical strength. The release of FITC-dextran from the printed systems was affected by both the ink composition and the post-processing step, enabling different drug release profiles over durations of up to three months.