Novel 3D Printed Modular Tablets Containing Multiple Anti-Viral Drugs: a Case of High Precision Drop-on-Demand Drug Deposition

Abstract

3D printed drug delivery systems have gained tremendous attention in pharmaceutical research due to their inherent benefits over conventional systems, such as provisions for customized design and personalized dosing. The present study demonstrates a novel approach of drop-on-demand (DoD) droplet deposition to dispense drug solutions precisely on binder jetting-based 3D printed multi-compartment tablets containing 3 model anti-viral drugs (hydroxychloroquine sulfate - HCS, ritonavir and favipiravir). The printing pressure affected the printing quality whereas the printing speed and infill density significantly impacted the volume dispersed on the tablets. Additionally, the DoD parameters such as nozzle valve open time and cycle time affected both dispersing volume and the uniformity of the tablets. The solid-state characterization, including DSC, XRD, and PLM, revealed that all drugs remained in their crystalline forms. Advanced surface analysis conducted by microCT imaging as well as Artificial Intelligence (AI)/Deep Learning (DL) model validation showed a homogenous drug distribution in the printed tablets even at ultra-low doses. For a four-hour in vitro drug release study, the drug loaded in the outer layer was released over 90%, and the drug incorporated in the middle layer was released over 70%. In contrast, drug encapsulated in the core was only released about 40%, indicating that outer and middle layers were suitable for immediate release while the core could be applied for delayed release. Overall, this study demonstrates a great potential for tailoring drug release rates from a customized modular dosage form and developing personalized drug delivery systems coupling different 3D printing techniques. Graphical Abstract: [Figure not available: see fulltext.]