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Comparative Study
. 2021 Mar 4;73(2):152-160.
doi: 10.1093/jpp/rgaa037.

Oral drug delivery systems using core-shell structure additive manufacturing technologies: a proof-of-concept study

Jiaxiang Zhang  1 , Pengchong Xu  1 , Anh Q Vo  1 , Michael A Repka  1   2
Affiliations
Comparative Study

Oral drug delivery systems using core-shell structure additive manufacturing technologies: a proof-of-concept study

Jiaxiang Zhang et al. J Pharm Pharmacol. .

Abstract

Objectives: The aim of this study was to couple fused deposition modelling 3D printing with melt extrusion technology to produce core-shell-structured controlled-release tablets with dual-mechanism drug-release performance in a simulated intestinal fluid medium. Coupling abovementioned technologies for personalized drug delivery can improve access to complex dosage formulations at a reasonable cost. Compared with traditional pharmaceutical manufacturing, this should facilitate the following: (1) the ability to manipulate drug release by adjusting structures, (2) enhanced solubility and bioavailability of poorly water-soluble drugs and (3) on-demand production of more complex structured dosages for personalized treatment.

Methods: Acetaminophen was the model drug and the extrusion process was evaluated by a series of physicochemical characterizations. The geometries, morphologies, and in vitro drug-release performances were compared between directly compressed and 3D-printed tablets.

Key findings: Initially, 3D-printed tablets released acetaminophen more rapidly than directly compressed tablets. Drug release became constant and steady after a pre-determined time. Thus, rapid effectiveness was ensured by an initially fast acetaminophen release and an extended therapeutic effect was achieved by stabilizing drug release.

Conclusions: The favourable drug-release profiles of 3D-printed tablets demonstrated the advantage of coupling HME with 3D printing technology to produce personalized dosage formulations.

Keywords: 3D-printed tablets; acetaminophen; drug delivery systems; hot melt extrusion; oral delivery improvement; patient-focused dosages.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Optimization of oral drug administration via hot melt extrusion/3D printing technologies.
Figure 2
Figure 2
Demonstration of the shell and core structure of the 3D design.
Figure 3
Figure 3
(a) Thermogravimetric analysis graphs of the raw materials: acetaminophen (APAP), hydroxypropylmethylcellulose (HPMC) E5, and HPMC acetate succinate (HPMCAS) HG; (b) Differential scanning calorimetry graphs of the APAP, physical mixture (PM) formulations and extruded (EXT) formulations.
Figure 4
Figure 4
Polarized light hot stage microscopy images monitoring the heating of the physical mixtures of (a) acetaminophen (APAP) and hydroxypropylmethylcellulose acetate succinate (HPMCAS) HG; and (b) APAP and HPMC E5 up to 220°C.
Figure 5
Figure 5
The extrusion torque and die pressure for different extrusion formulations.
Figure 6
Figure 6
Scanning electron microscopy images show (a) the surface of the hydroxypropylmethylcellulose (HPMC) and HPMC acetate succinate (HPMCAS) filaments. Rectangles in the upper images indicate the positions of enlarged images shown below. Magnification and scale bar are shown at the bottom of each image; (b) the porous structure of the shell (left) and the compact core (right) of the 3D-printed tablets; (c) the direct compressed HPMCAS matrix and HPMC matrix tablets.
Figure 7
Figure 7
Drug-release profiles of 3D-printed tablets (3DP: core–shell-structured tablets; 3DPS: shell structure only; 3DPC: core structure only) and directly compressed tablets (TS: hydroxypropylmethylcellulose (HPMC) matrix; TC: HPMC acetate succinate (HPMCAS) matrix) provided in relative (%) amounts.
See this image and copyright information in PMC

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