Additive Manufacturing of an Extended-Release Tablet of Tacrolimus

Abstract

An extended-release tablet of tacrolimus as once-daily dosing was fabricated using 3D printing technology. It was developed by combining two 3D-printing methods in parallel. Indeed, an optimized mixture of PVA, sorbitol, and magnesium stearate as a shell compartment was printed through a hot-melt extrusion (HME) nozzle while an HPMC gel mixture of the drug in the core compartment was printed by a pressure-assisted micro-syringe (PAM). A 3D-printed tablet with an infill of 90% was selected as an optimized formula upon the desired dissolution profile, releasing 86% of the drug at 12 h, similar to the commercial one. The weight variation, friability, hardness, assay, and content uniformity determination met USP requirements. A microbial evaluation showed that the 3D-printed tablet does not support microbial growth. SEM analysis showed smooth surfaces with multiple deposited layers. No peak interference appeared based on FTIR analysis. No decomposition of the polymer and drug was observed in the printing temperature, and no change in tacrolimus crystallinity was detected based on TGA and DSC analyses, respectively. The novel, sTable 3D-printed tablet, fabricated using controllable additive manufacturing, can quickly provide tailored dosing with specific kinetic release for personalized medicine at the point-of-care.

Status of Polymer Fused Deposition Modeling (FDM)-Based Three-Dimensional Printing (3DP) in the Pharmaceutical Industry

“…Conversely, the use of poorly permeable hydrophobic polymers such as EDR RL and EC often results in an extremely slow release of the drug [61]. Similarly, other agents, like "Ticagrelor", a blood-thinning drug, and "Tacrolimus", a macrolide inhibitor of calcineurin used in organ transplantations, have also been developed using 3DP techniques [62,63]. In addition, another slow-release drug, in the form of pH-responsive tablets for colon drug-delivery applications, have been developed through the use of 3DP technology [64].…”

Magnesium Hydroxide as a Versatile Nanofiller for 3D-Printed PLA Bone Scaffolds

“…Three-dimensional printing technologies, based on the principle of discrete accumulation, could theoretically realize the precise forming of complex structures, which could accurately meet the controllable building of porous structures and personalized shapes for bone scaffolds [ 30 , 31 ]. Due to the wide range of processable materials, low material and use cost, environmental protection, and nontoxicity, fused deposition modeling (FDM), as the most common 3D printing technology, offers the potential for design and manufacturing in the combination of polymers and the biomedical field [ 32 , 33 ]. Furthermore, FDM has shown obvious competitiveness in the preparation of biodegradable polymer bone scaffolds including PLA [ 34 , 35 , 36 ].…”

Fabrication of a Controlled-Release Core-Shell Floating Tablet of Ketamine Hydrochloride Using a 3D Printing Technique for Management of Refractory Depressions and Chronic Pain

“…In recent years, there has been a surge in pharmaceutical manufacturing via 3D printing, often referred to as “3D pharming” [ 21 ]. 3D printing in pharmaceuticals holds potential for incorporating multiple drug substances with varying doses within a single pill, managing drug release kinetics through formulation adjustments, and tailoring drug dosage to match the pharmacokinetic profile [ 22 ].…”

“…Fused deposition modelling (FDM) 3D printing is the most common method used in pharmaceutical applications due to the more significant number of biocompatible excipients, lower cost of necessary equipment, ability to create complex dosage forms, and easier production process [ 23 ]. Recently, producing filaments as well as 3D printing objects have been facilitated using the hot-melt extrusion (HME)-based 3D printing approach to fabricate pills with desired properties [ 22 ]. This method has allowed not only the mixing of diverse thermoset polymers in melt extrusion processes but also higher drug loading capacity, compared to the FDM-based 3D printing method.…”