Three-Dimensional Printing of Personalized Carbamazepine Tablets Using Hydrophilic Polymers: An Investigation of Correlation Between Dissolution Kinetics and Printing Parameters
Abstract
1. Introduction
2. Materials and Methods
2.1. Materials
2.2. Methods
2.2.1. Process Development of 3D-Printed Tablets
HME
Three-Dimensional Printing
Process Development Using Design of Experiments (DoE)
2.2.2. Characterization of Raw Materials, Intermediate Extrudates, and Printed Tablets
Thermalgravimetric Analysis (TGA)
Differential Scanning Calorimetry (DSC)
Powder X-Ray Diffraction (PXRD)
Hot-Stage Polarized Light Microscopy (PLM)
Qualification and Quantification of CBZ Using HPLC
2.2.3. In Vitro Drug Release Study
3. Results and Discussion
3.1. Thermal Stability
3.2. Preparation of 3D Printable Filaments
3.3. Solid-State Analysis
3.3.1. Characterization of Thermal Behavior of Raw Materials and Filaments
3.3.2. Hot-Staged PLM of Raw Materials and Filaments
3.3.3. Characterization of Crystalline States of Raw Materials and Filaments
3.4. DoE Studies
3.4.1. Physical Properties of 3D-Printed Tablets
Morphology Study
Height and Diameter
Mass
3.4.2. In Vitro Drug Release Studies
Quality and Quantity of the CBZ
In Vitro Drug Release Studies of 3D-Printed Tablets
Analysis of Q4h and t50%
Response Surface Methodology
The Release Kinetics
3.5. Reproducibility
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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# | F | T | S | Diameter | RSD 1 | RSD 2 | Height | RSD 1 | RSD 2 | Mass | RSD 1 |
---|---|---|---|---|---|---|---|---|---|---|---|
(%) | (°C) | (mm/s) | (mm) | % | (mm) | % | (mg) | % | |||
R1 | 20 | 40 | 60 | 12.15 ± 0.07 | 0.58 | 1.25 | 4.97 ± 0.12 | 2.41 | −0.60 | 374.3 ± 8.6 | 2.30 |
R2 | 60 | 60 | 60 | 12.03 ± 0.10 | 0.83 | 0.25 | 4.95 ± 0.09 | 1.82 | −1.00 | 402.3 ± 15.5 | 3.85 |
R3 | 60 | 60 | 60 | 12.08 ± 0.13 | 1.08 | 0.67 | 5.05 ± 0.02 | 0.40 | 1.00 | 403.7 ± 15.0 | 3.72 |
R4 | 100 | 80 | 60 | 12.07 ± 0.09 | 0.75 | 0.58 | 5.07 ± 0.04 | 0.79 | 1.40 | 386.3 ± 17.6 | 4.56 |
R5 | 60 | 60 | 60 | 12.12 ± 0.12 | 0.99 | 1.00 | 4.95 ± 0.02 | 0.40 | −1.00 | 402.0 ± 15.1 | 3.76 |
R6 | 60 | 80 | 100 | 12.04 ± 0.05 | 0.42 | 0.33 | 5.02 ± 0.04 | 0.80 | 0.40 | 394.0 ± 17.3 | 4.39 |
R7 | 100 | 60 | 20 | 12.20 ± 0.08 | 0.66 | 1.67 | 5.08 ± 0.02 | 0.39 | 1.60 | 425.7 ± 21.0 | 4.93 |
R8 | 60 | 80 | 20 | 12.24 ± 0.14 | 1.14 | 2.00 | 5.08 ± 0.02 | 0.39 | 1.60 | 412.0 ± 11.0 | 2.67 |
R9 | 20 | 60 | 20 | 12.07 ± 0.07 | 0.58 | 0.58 | 5.07 ± 0.03 | 0.59 | 1.40 | 416.3 ± 17.0 | 4.08 |
R10 | 20 | 80 | 60 | 12.17 ± 0.10 | 0.82 | 1.42 | 5.06 ± 0.10 | 1.98 | 1.20 | 420.3 ± 9.5 | 2.26 |
R11 | 100 | 40 | 60 | 12.07 ± 0.05 | 0.41 | 0.58 | 4.96 ± 0.17 | 3.43 | −0.80 | 420.0 ± 3.0 | 0.71 |
R12 | 60 | 40 | 100 | 12.00 ± 0.12 | 1.00 | 0.00 | 4.92 ± 0.03 | 0.61 | −1.60 | 419.7 ± 16.8 | 4.00 |
R13 | 60 | 40 | 20 | 12.25 ± 0.02 | 0.16 | 2.08 | 4.90 ± 0.04 | 0.82 | −2.00 | 418.7 ± 11.1 | 2.65 |
R14 | 20 | 60 | 100 | 11.96 ± 0.11 | 0.92 | −0.33 | 4.88 ± 0.02 | 0.41 | −2.40 | 408.0 ± 21.1 | 5.17 |
R15 | 100 | 60 | 100 | 11.89 ± 0.16 | 1.35 | −0.92 | 4.94 ± 0.01 | 0.20 | −1.20 | 391.7 ± 9.1 | 2.32 |
Average | 12.09 | 4.99 | 406.33 | ||||||||
LCL | 11.79 | 4.78 | 361.99 | ||||||||
UCL | 12.39 | 5.21 | 450.67 |
Group | F (%) | T (°C) | S (mm/s) | Q4h (%) | t50% (min) |
---|---|---|---|---|---|
R1 | 20 | 40 | 60 | 45.49 | 245 |
R2 | 60 | 60 | 60 | 49.63 | 240 |
R3 | 60 | 60 | 60 | 47.77 | 255 |
R4 | 100 | 80 | 60 | 46.59 | 260 |
R5 | 60 | 60 | 60 | 48.36 | 250 |
R6 | 60 | 80 | 100 | 49.17 | 245 |
R7 | 100 | 60 | 20 | 28.72 | 510 |
R8 | 60 | 80 | 20 | 32.18 | 430 |
R9 | 20 | 60 | 20 | 31.35 | 435 |
R10 | 20 | 80 | 60 | 48.36 | 250 |
R11 | 100 | 40 | 60 | 26.96 | 245 |
R12 | 60 | 40 | 100 | 37.18 | 335 |
R13 | 60 | 40 | 20 | 28.62 | 530 |
R14 | 20 | 60 | 100 | 40.86 | 290 |
R15 | 100 | 60 | 100 | 49.82 | 240 |
F | T | S | F * × T | F × S | T × S | F2 | T2 | S2 | |
---|---|---|---|---|---|---|---|---|---|
p-value | 0.8234 | 0.0608 | 0.0002 | 0.5857 | 0.1749 | 0.8744 | 1.0000 | 0.6001 | 0.0005 |
Significance | NS | NS | *** | NS | NS | NS | NS | NS | *** |
Code Equation | t50% = 0.21761 − 0.011099 × S + 0.00041 × S2 |
F | T | S | F × T | F × S | T × S | F2 | T2 | S2 | |
---|---|---|---|---|---|---|---|---|---|
p-value | 0.5282 | 0.0935 | 0.0005 | 0.4435 | 0.0911 | 0.3680 | 0.9990 | 0.5901 | 0.0005 |
Significance | NS | NS | *** | NS | NS | NS | NS | NS | *** |
Code Equation | 1/Sqrt(Q4h) = 692.34375 − 64.86486 × S + 2.29410 × S2 |
# | Zero-Order | First-Order | Higuchi | Korsmeyer–Peppas | Peppas–Sahlin | ||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
K0 | R2 | k | R2 | k | R2 | kkp | n | R2 | k1 | k2 | m | R2 | |
CBZ | 0.187 | 0.8436 | 0.010 | 0.9982 | 4.470 | 0.9423 | 9.396 | 0.377 | 0.9588 | 3.153 | −0.024 | 0.675 | 0.9911 |
PM | 0.192 | 0.8036 | 0.014 | 0.9973 | 4.666 | 0.9182 | 14.387 | 0.313 | 0.9516 | 5.524 | −0.073 | 0.595 | 0.9884 |
EXT | 0.154 | 0.9555 | 0.004 | 0.9989 | 3.514 | 0.9896 | 2.303 | 0.570 | 0.9891 | 0.532 | −0.001 | 0.895 | 0.9994 |
R1 | 0.122 | 0.9579 | 0.002 | 0.9938 | 2.797 | 0.9908 | 1.860 | 0.567 | 0.9905 | 0.458 | −0.001 | 0.880 | 0.9995 |
R2 | 0.123 | 0.9341 | 0.002 | 0.9840 | 2.841 | 0.9842 | 2.713 | 0.508 | 0.9839 | 0.683 | −0.002 | 0.829 | 0.9983 |
R3 | 0.122 | 0.9420 | 0.002 | 0.9874 | 2.817 | 0.9868 | 2.456 | 0.523 | 0.9863 | 0.616 | −0.001 | 0.841 | 0.9988 |
R4 | 0.127 | 0.9493 | 0.002 | 0.9915 | 2.916 | 0.9850 | 1.933 | 0.568 | 0.9844 | 0.321 | 0.000 | 0.956 | 0.9993 |
R5 | 0.120 | 0.9483 | 0.002 | 0.9880 | 2.753 | 0.9869 | 2.082 | 0.546 | 0.9863 | 0.549 | −0.001 | 0.850 | 0.9966 |
R6 | 0.130 | 0.9493 | 0.003 | 0.9928 | 2.984 | 0.9866 | 2.073 | 0.560 | 0.9859 | 0.419 | −0.001 | 0.913 | 0.9990 |
R7 | 0.092 | 0.9889 | 0.001 | 0.9978 | 2.073 | 0.9908 | 0.707 | 0.676 | 0.9976 | 0.499 | 0.475 | 0.362 | 0.9977 |
R8 | 0.103 | 0.9874 | 0.002 | 0.9988 | 2.320 | 0.9918 | 0.775 | 0.680 | 0.9980 | −0.699 | 1.100 | 0.319 | 0.9980 |
R9 | 0.102 | 0.9844 | 0002 | 0.9972 | 2.295 | 0.9908 | 0.868 | 0.660 | 0.9961 | −0.406 | 1.062 | 0.318 | 0.9961 |
R10 | 0.132 | 0.9592 | 0.003 | 0.9953 | 3.018 | 0.9895 | 2.125 | 0.558 | 0.9896 | 0.515 | −0.001 | 0.872 | 0.9980 |
R11 | 0.115 | 0.9217 | 0.002 | 0.9739 | 2.675 | 0.9787 | 3.073 | 0.477 | 0.9796 | 0.695 | −0.002 | 0.824 | 0.9982 |
R12 | 0.126 | 0.9834 | 0.002 | 0.9966 | 2.811 | 0.9857 | 0.746 | 0.717 | 0.9933 | −2.620 | 1.893 | 0.303 | 0.9938 |
R13 | 0.093 | 0.9909 | 0.001 | 0.9986 | 2.093 | 0.9933 | 0.772 | 0.664 | 0.9996 | 1.004 | 0.282 | 0.391 | 0.9997 |
R14 | 0.136 | 0.9757 | 0.003 | 0.9954 | 3.043 | 0.9847 | 0.979 | 0.686 | 0.9897 | −5.017 | 3.366 | 0.270 | 0.9907 |
R15 | 0.143 | 0.9605 | 0.003 | 0.9965 | 3.241 | 0.9871 | 1.764 | 0.600 | 0.9875 | 0.296 | 0.000 | 0.980 | 0.9991 |
# | Zero-Order | First-Order | Higuchi | Korsmeyer–Peppas | Peppas–Sahlin | ||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
K0 | R2 | k | R2 | k | R2 | kkp | n | R2 | k1 | k2 | m | R2 | |
R1 | 0.201 | 0.9944 | 0.003 | 0.9982 | 2.552 | 0.9790 | 0.704 | 0.760 | 0.9984 | 1.039 | 0.151 | 0.485 | 0.9988 |
R2 | 0.224 | 0.9893 | 0.003 | 0.9970 | 2.856 | 0.9812 | 0.900 | 0.734 | 0.9968 | 0.452 | 0.662 | 0.388 | 0.9968 |
R3 | 0.215 | 0.9909 | 0.003 | 0.9976 | 2.744 | 0.9821 | 0.879 | 0.731 | 0.9977 | 0.886 | 0.406 | 0.418 | 0.9979 |
R4 | 0.205 | 0.9957 | 0.003 | 0.9982 | 2.589 | 0.9764 | 0.635 | 0.784 | 0.9985 | 0.999 | 0.116 | 0.509 | 0.9990 |
R5 | 0.214 | 0.9972 | 0.003 | 0.9949 | 2.674 | 0.9666 | 0.501 | 0.837 | 0.9967 | 0.894 | 0.048 | 0.580 | 0.9980 |
R6 | 0.217 | 0.9952 | 0.003 | 0.9978 | 2.734 | 0.9748 | 0.634 | 0.795 | 0.9979 | 0.925 | 0.177 | 0.486 | 0.9982 |
R7 | 0.218 | 0.9896 | 0.002 | 0.9924 | 1.653 | 0.9843 | 0.745 | 0.662 | 0.9954 | 1.013 | 0.075 | 0.479 | 0.9974 |
R8 | 0.143 | 0.9921 | 0.002 | 0.9957 | 1.831 | 0.9814 | 0.637 | 0.714 | 0.9970 | 0.931 | 0.084 | 0.492 | 0.9981 |
R9 | 0.142 | 0.9884 | 0.002 | 0.9926 | 1.831 | 0.9824 | 0.790 | 0.671 | 0.9946 | 1.084 | 0.105 | 0.466 | 0.9961 |
R10 | 0.214 | 0.9918 | 0.003 | 0.9923 | 2.735 | 0.9769 | 1.010 | 0.702 | 0.9932 | 1.452 | 0.098 | 0.504 | 0.9957 |
R11 | 0.220 | 0.9931 | 0.003 | 0.9963 | 2.810 | 0.9818 | 0.968 | 0.716 | 0.9975 | 1.426 | 0.099 | 0.509 | 0.9988 |
R12 | 0.161 | 0.9965 | 0.002 | 0.9944 | 2.018 | 0.9652 | 0.396 | 0.828 | 0.9952 | 0.686 | 0.030 | 0.592 | 0.9974 |
R13 | 0.130 | 0.9847 | 0.002 | 0.9899 | 1.697 | 0.9915 | 0.951 | 0.618 | 0.9978 | 1.220 | 0.105 | 0.447 | 0.9991 |
R14 | 0.177 | 0.9970 | 0.002 | 0.9953 | 2.222 | 0.9666 | 0.439 | 0.826 | 0.9961 | 0.766 | 0.037 | 0.583 | 0.9979 |
R15 | 0.217 | 0.9964 | 0.003 | 0.9970 | 2.739 | 0.9738 | 0.649 | 0.790 | 0.9977 | 1.072 | 0.076 | 0.542 | 0.9987 |
# | F | T | S | Diameter | Height | Mass | Q4h | t50% |
---|---|---|---|---|---|---|---|---|
(%) | (°C) | (mm/s) | (mm) | (mm) | (mg) | (%) | (min) | |
R2 | 60 | 12.03 ± 0.10 | 4.95 ± 0.09 | 402.3 ± 15.5 | 49.63 | 240 | ||
R3 | 60 | 60 | 12.08 ± 0.13 | 5.05 ± 0.02 | 403.7 ± 15.0 | 47.77 | 255 | |
R5 | 12.12 ± 0.12 | 4.95 ± 0.02 | 402.0 ± 15.1 | 48.36 | 250 | |||
Average | 12.08 | 4.98 | 402.67 | 48.59 | 248.3 | |||
S.D. | 0.05 | 0.06 | 0.91 | 0.95 | 7.6 | |||
RSD 1 | 0.37 | 1.16 | 0.23 | 1.96 | 3.06 | |||
RSD 2 | 0.38 | 1.15 | NA | NA | NA |
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Huang, L.; Zhang, X.; Huang, Q.; Zhu, M.; Yang, T.; Zhang, J. Three-Dimensional Printing of Personalized Carbamazepine Tablets Using Hydrophilic Polymers: An Investigation of Correlation Between Dissolution Kinetics and Printing Parameters. Polymers 2025, 17, 2126. https://doi.org/10.3390/polym17152126
Huang L, Zhang X, Huang Q, Zhu M, Yang T, Zhang J. Three-Dimensional Printing of Personalized Carbamazepine Tablets Using Hydrophilic Polymers: An Investigation of Correlation Between Dissolution Kinetics and Printing Parameters. Polymers. 2025; 17(15):2126. https://doi.org/10.3390/polym17152126
Chicago/Turabian StyleHuang, Lianghao, Xingyue Zhang, Qichen Huang, Minqing Zhu, Tiantian Yang, and Jiaxiang Zhang. 2025. "Three-Dimensional Printing of Personalized Carbamazepine Tablets Using Hydrophilic Polymers: An Investigation of Correlation Between Dissolution Kinetics and Printing Parameters" Polymers 17, no. 15: 2126. https://doi.org/10.3390/polym17152126
APA StyleHuang, L., Zhang, X., Huang, Q., Zhu, M., Yang, T., & Zhang, J. (2025). Three-Dimensional Printing of Personalized Carbamazepine Tablets Using Hydrophilic Polymers: An Investigation of Correlation Between Dissolution Kinetics and Printing Parameters. Polymers, 17(15), 2126. https://doi.org/10.3390/polym17152126