(T1430-06-36) Exploration of FDM 3D-Printed Multi-Compartment Drug Delivery Devices: Structural Modulation of Release Kinetics for Personalized Therapy

Purpose: Three-dimensional printing (3DP) overcomes traditional manufacturing constraints by enabling complex, customized fabrication through layer-by-layer construction from digital files. In the pharmaceutical industry, 3DP enables personalized medicine and point-of-care production in hospitals, pharmacies, and communities. It allows for flexible small-batch production and supports precise adjustments to drug dosages, release profiles, and combination therapies, making it ideal for individualized treatments and small-scale clinical trial preparations.[1] The drug release pattern (e.g., pulsatile versus sustained release) critically effects clinical outcomes. Pulsatile drug delivery systems can significantly enhance the therapeutic efficacy of medications like GLP-1 analogs and insulin by improving oral bioavailability through controlled release mechanisms. These systems maintain optimal concentrations for short-acting drugs (e.g., antibiotics, nitroglycerin) while optimizing release profiles for chronotherapy in neurological disorders including Parkinson's disease and ADHD.[2] Our study aimed to develop novel 3D printed modular drug delivery devices (including capsules and tablets) that enable precise drug delivery such as flexible adjustments of dosing regimens and release kinetics that are controlled by geometric designs. Featuring tunable structures with both snap-fit and screw-thread assembly mechanisms, these devices permit effortless, tool-free and adhesive-less assembly after drug loading. We evaluated their drug release behaviors to elucidate critical structure-release correlations. This work establishes a foundation for adaptable, personalized dosing strategies and demonstrates the clinical potential of these easily configurable, 3D-printed pharmaceutical devices for precision medicine applications.

Methods: Device Design and Preparation: Multi-compartment capsular and tablet devices were designed using Autodesk Fusion 360. All devices were fabricated via fused deposition modeling (FDM) using a Bambu Lab A1 mini printer equipped with a commercial polyvinyl alcohol (PVA) filament (Ø 1.75 mm). Dissolution Testing and Visualization: To facilitate real-time visual dissolution monitoring, three water-soluble dyes—tartrazine, cresol red, and methylene blue—were incorporated into the printed devices. Caffeine was selected as a model drug for quantitative dissolution analysis. The dissolution behavior was evaluated according to the United States Pharmacopeia (USP) Apparatus 2. The dissolution medium consisted of 900 mL of deionized water maintained at 37 ± 0.5 °C with a paddle rotation speed of 50 rpm. Samples were withdrawn at predetermined time points and analyzed by ultraviolet spectroscopy to determine drug release kinetics.

Results: Characterization of PVA Filament Dissolution Properties: Prior to device fabrication, the dissolution behavior of the polyvinyl alcohol (PVA) filament was systematically evaluated. As illustrated in Figure 1A, test specimens were designed with water-insoluble polyethylene terephthalate glycol (PETG) forming the side and base walls, while the top surface consisted of PVA to maintain consistent contact area (0.785 cm²) with the dissolution medium. The fabricated PVA disks (Figure 1B) underwent dissolution testing in deionized water using USP Apparatus 2 (Figure 1C) at 37.0 ± 0.5°C with 50 rpm paddle agitation. The measured PVA mass loss at 30, 60, 90, and 120-minute intervals was converted to equivalent thickness reduction based on the constant surface area and material density (Figure 1D) demonstrated linear dissolution kinetics (R² = 0.9666) under these conditions. These results means that the dissolution characteristics of PVA can be utilized to design drug delivery devices with precisely controlled release time points. Design of Multi‑Compartment Capsular and Tablet Devices: Our design hypothesis proposed that precise control over drug release timing could be achieved by strategically varying the thickness of critical structural elements while maintaining complete water-tight integrity. Based on this principle, we developed three multi-compartment capsule designs with differential wall thicknesses (Figure 2): (A) dual-chamber: 0.5 mm (immediate)/1.0 mm (delayed) walls, (B) dual-chamber: 0.5 mm/1.5 mm walls, (C) triple-chamber: 0.5/1.0/1.5 mm sequential walls; and tablets: (D) three-layer with 1.0 mm uniform walls, (E) gradient-base with 0.25-1.0 mm ramped thickness. For each device, cross-sectional schematics, CAD renderings, and photographs of printed prototypes are provided, confirming successful fabrication, with leak-proof assembly confirmed in testing. Structural details were verified through microscope (Figure 2F), while manufacturing precision was quantified by variability of the measured weights (RSD < 1%) as shown in Figure 2G. Dissolution Study of 3D-Printed Drug Devices: The five 3D-printed devices were loaded with different colored dyes in separate chambers to qualitatively observe and record the dissolution state of each compartment at various time points. Concurrently, caffeine was employed as a water-soluble model drug for quantitative determination of dissolution profiles (Figure 3A-E). Experimental results confirmed our initial hypothesis that precise control over drug release timing could be achieved by strategically varying the thickness of critical structural elements while maintaining complete water-tight integrity. Devices A-D demonstrated well-reproducible pulsatile release patterns, while Device E with its sloped base structure exhibited near-zero-order release kinetics. These findings establish a fundamental basis for subsequent personalized customization of drug-loaded devices.

Conclusion: Our study demonstrated the potential of FDM, for designing and fabricating multi-compartment drug delivery devices with precise control over drug release profiles. By varying the thickness of structural elements, we established a correlation between designment and release behavior, creating devices that meet individualized therapeutic needs.

References: 1. Ventola, C.L., Medical Applications for 3D Printing: Current and Projected Uses. P t, 2014. 39(10): p. 704-11.
2. Jain, D., et al., Recent technologies in pulsatile drug delivery systems. Biomatter, 2011. 1(1): p. 57-65.

Acknowledgements: The authors gratefully acknowledge funding from NIST SBIR Phase II grant #70NANB23H209.


Figure 1. Characterization of PVA filament dissolution properties. (A) Schematic design of the dissolution test specimen with PETG side/base walls and PVA top surface (diameter: 1 cm). (B) Photograph of the fabricated PVA disk specimen. (C) Dissolution testing setup using USP Apparatus II (paddle method) in 900 mL deionized water at 37.0 ± 0.5°C with 50 rpm agitation. (D) PVA thickness loss profile showing linear dissolution kinetics (R² = 0.9666) over 120 minutes. Error bars represent standard deviation (n=5).


Figure 2. Design and characterization of multi-compartment capsular and tablet devices. (A) Dual-chamber capsule with 0.5 mm (immediate release) and 1.0 mm (delayed release) wall thicknesses. (B) Dual-chamber capsule with 0.5 mm and 1.5 mm differential wall thicknesses. (C) Triple-chamber capsule with sequential 0.5 mm, 1.0 mm, and 1.5 mm walls. (D) Three-layer tablet with uniform 1.0 mm peripheral walls. (E) Gradient-base tablet with ramped bottom thickness (0.25-1.0 mm). For each device (A-E), from left to right: cross-sectional schematic highlighting thickness parameters, CAD rendering, and photograph of the as-printed device (pre-assembly and post-assembly). (F) Microscope images showing structural details of representative devices. (G) Weight measurements demonstrating manufacturing precision (RSD < 1%, n=5).


Figure 3. Controlled drug release from 3D-printed devices. (A) Dual-chamber capsule (0.5 mm immediate-release/1.0 mm delayed-release walls), (B) Dual-chamber capsule (0.5 mm/1.5 mm walls), (C) Triple-chamber capsule (0.5/1.0/1.5 mm sequential walls), (D) Three-layer tablet (uniform 1.0 mm walls), (E) Gradient-base tablet (0.25-1.0 mm ramped bottom). Bottom panels: Devices loaded with color-coded dyes showing compartment-specific dissolution. Top panels: Corresponding caffeine release profiles demonstrating (i) pulsatile release (Devices A-D) and (ii) near-zero-order kinetics (Device E).(n=3)