(T1130-07-40) Development of Mathematical Function Control-Based 3D Printed Tablets and Effect on Drug Release

Purpose: The study aimed to apply mathematical surface equations to construct 3D-printed tablet models using water-soluble polymer (polyvinyl alcohol, PVA) and evaluate the impact of functional parameters on in vitro drug release behavior. This approach is intended to improve the precision, reproducibility, and predictability of drug release profiles by leveraging advanced 3D printing techniques coupled with hot melt extrusion (HME). By utilizing these techniques, the study aimed to develop personalized drug delivery systems with optimized dissolution rates and enhanced patient compliance.

Methods: Acetaminophen (APAP) was used as the model drug, constituting 15% (w/w) of the formulation, with PVA comprising 85% (w/w). Filaments were prepared using a co-rotating twin-screw extruder at 160°C and printed using a Prusa i3 MK3 3D printer. Five tablet designs (T1 to T5) were modeled using parabolic surface equations with varying depths of curvature (b = 4, 2, 0, -2, -4 mm). These designs were converted into STL files for 3D printing. The printed tablets were characterized using differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM). In vitro drug release was assessed using USP dissolution apparatus II, with a paddle rotation speed set to 50 rpm and a pH 6.8 phosphate buffer as the dissolution medium. Samples were collected at various time points for analysis using high-performance liquid chromatography (HPLC). The release kinetics were analyzed using zero-order, first-order, Hixson-Crowell, and Ritger-Peppas equations to determine the mechanisms that regulate drug release.

Results: The DSC thermograms indicated successful dispersion of APAP within the PVA matrix, with the absence of the characteristic melting peak of APAP suggesting the formation of an amorphous solid dispersion (Figure 2A). FTIR analysis confirmed no significant chemical interactions between APAP and PVA during the printing process, as evidenced by the unchanged characteristic peaks of APAP and PVA in the spectra. SEM images revealed uniform internal structures with minimal gaps, demonstrating the efficacy of 100% infill density in producing compact and homogeneous tablets (Figure 1). The cross-sections of the tablets showed smooth surfaces without large individual particles, indicating precise layer-by-layer construction. The in vitro drug release profiles showed that tablets with higher curvature (T5) had the fastest dissolution rates, correlating with their larger surface areas (Figure 2B). Specifically, T5 exhibited complete drug release within 4 hours, while T1 and T2 took approximately 6 hours. The drug release kinetics fitted well with first-order, Hixson-Crowell, and Ritger-Peppas models, indicating a combination of erosion and diffusion mechanisms. Quadratic regression analysis showed a strong correlation between the dissolution curves and the surface area parameters, with R² values exceeding 0.8 for both linear and quadratic regressions.

Conclusion: The study successfully demonstrated the use of mathematical surface equations to design and produce precise and reproducible 3D-printed tablets. This approach allows for controlled drug release by adjusting tablet geometry and surface characteristics. The findings highlight the potential of 3D printing in personalized medicine, enabling tailored drug delivery systems with predictable release profiles. Future research could explore the application of this method to a broader range of drugs and dosage forms.

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3. Darwesh A.Y., et al. Advanced 3D Electrospinning “Xspin” System: Fabrication of Bifiber Floating Oral Pharmaceutical Scaffolds for Controlled Drug Delivery. Mol. Pharmaceutics, 2024.
4. Karami T., et al. 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. Polymers, 2024.
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Table 1 - Theoretical mathematical values and 3D software calculation values of tablet

Figure 1 - A. The top and side views of 5 types of 3D printed tablets , B. SEM images of the cross-section of the printed tablet at × 50 magnification level. (a) the edge of the tablet sample. (b) the center of the tablet sample

Figure 2 - A. . DSC thermogram of acetaminophen, PVA, physical mixture and printed tablets, B. The dissolution profiles of 3D printed tablets