Application and Multi-Stage Optimization of Daylight Polymer 3D Printing of Personalized Medicine Products
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials
2.2. Optimization of Formulation
- Evaluation of PEGDA/PEG/water ratio: different amounts of PEGDA MW 575, PEG 400, and water with 0.1% addition of riboflavin were tested in PVC molds to optimize photosensitive resin curable with visible light. The compositions of the tested formulations were selected based on the full factorial design of the experiment.
- 3D printing of placebo tablets and printer customization: optimized resin was used to print placebo tablets using a Daylight Polymer Printing technology. To improve the quality of the printed tablets and reduce the amount of resin needed for printing, an overlay on the printer’s platform and a smaller resin tank with an adapted holder were used.
- Assessment of the impact of co-initiators: the best resin composition was used to evaluate the effectiveness of ascorbic acid and triethanolamine to improve the mechanical properties of the tablets and reduce the printing time.
- Evaluation of the possibility of reusing the uncured resin left over from printing.
- 3D printing of drug-loaded tablets: process optimization and analysis.
2.3. Evaluation of PEGDA/PEG/Water Ratio
2.4. Mechanical Properties
2.5. Model-Driven Optimization of Resin Composition
2.6. 3D Printing of Placebo Tablets
2.7. Assessment of the Impact of Co-Initiators
2.8. Evaluation of Resin Reusability
2.9. Preparation of Drug-Loaded Tablets
2.10. Drug Content in Tablets
2.11. Dissolution Study
2.12. Project Volume–Dosage Correlation
3. Results and Discussion
3.1. Optimization of Formulation
3.2. 3D Printing of Placebo Tablets and Customization of the 3D Printer
3.3. Co-Initiator Impact Assessment and Optimization of Printing Settings
3.4. Drug-Loaded Tablets
3.5. Project Volume–Dosage Correlation
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Name | Tested Formulation Composition (% w/w) | |||
---|---|---|---|---|
PEGDA 575 | PEG 400 | Water | Riboflavin | |
P1 | 15.00 (−1) | 79.90 | 5.00 (−1) | 0.10 |
P2 | 45.00 (0) | 49.90 | 5.00 (−1) | |
P3 | 75.00 (+1) | 29.90 | 5.00 (−1) | |
P4 | 15.00 (−1) | 69.90 | 15.00 (0) | |
P5 | 45.00 (0) | 39.90 | 15.00 (0) | |
P5′ | 45.00 (0) | 39.90 | 15.00 (0) | |
P5″ | 45.00 (0) | 39.90 | 15.00 (0) | |
P6 | 75.00 (+1) | 9.90 | 15.00 (0) | |
P7 | 15.00 (−1) | 59.90 | 25.00 (+1) | |
P8 | 45.00 (0) | 29.90 | 25.00 (+1) | |
P9 | 75.00 (+1) | - | 24.90 (+1) |
Name | Resin Composition (% w/w) | Printing Parameters | |||||
---|---|---|---|---|---|---|---|
PEGDA 575 | PEG 400 | Water | Riboflavin | Additional Compound | Layer Height (µm) | Exposure Time (s) | |
TP_100/200 | 45.00 | 39.90 | 15.00 | 0.10 | - | 100 | 200 |
TP_50/100 | 50 | 100 | |||||
TP_50/100′ | 50 | 100 | |||||
TP_AscA1_100/200 | 45.00 | 38.90 | 15.00 | 0.10 | AscA 1.00 | 100 | 200 |
TP_AscA2_100/200 | 45.00 | 39.40 | 15.00 | 0.10 | AscA 0.50 | 100 | 200 |
TP_AscA3_100/200 | 45.00 | 39.80 | 15.00 | 0.10 | AscA 0.10 | 100 | 200 |
TP_TRI_100/200 | 45.00 | 39.75 | 15.00 | 0.10 | TRI 0.15 | 100 | 200 |
TP_TRI_50/50 | 50 | 50 | |||||
TP_TRI_50/25 | 50 | 25 | |||||
TP_TRI_50/25′ | 50 | 25 | |||||
TP_TRI_50/12.5 | 50 | 12.5 |
Name | Layer Height (µm) | Exposure Time (s) |
---|---|---|
TMEB_50/25 | 50 | 25 |
TMEB_50/25′ | ||
TMEB_50/50 | 50 | 50 |
TMEB_50/50′ |
Name | Force (N) ± SD |
---|---|
P1 | 0.11 ± 0.02 |
P2 | 1.66 ± 0.23 |
P3 | resin uncured |
P4 | 0.11 ± 0.01 |
P5 | 2.05 ± 0.19 |
P5′ | 2.07 ± 0.44 |
P5″ | 2.13 ± 0.19 |
P6 | 0.98 ± 0.13 |
P7 | 0.09 ± 0.01 |
P8 | 1.00 ± 0.11 |
P9 | resin uncured |
First-Order Model | Second-Order Model | |
---|---|---|
Formula | Y = C1 × X1 + C2 × X2 + Intercept | Y = C1 × X1 + C2 × X2 + C3 × X1 × X2 + C4 × X12 + C5 × X22 + Intercept |
p-value | 0.9277 | 0.0046 |
Coefficients | Intercept = 0.9276 (p = 0.0159) C1 = 0.112 (p = 0.792) C2 = −0.115 (p = 0.788) | Intercept = 2.0294 (p = 5.94 × 10−5) C1 = 0.112 (p = 0.427) C2 = −0.115 (p = 0.417) C3 = 0.0057 (p = 0.973) C4 = −1.402 (p = 0.00091) C5 = −0.618 (p = 0.027) |
Residual standard error | 1.01 | 0.3179 |
Multiple R-squared | 0.0186 | 0.9393 |
Adjusted R-squared | −0.2268 | 0.8786 |
Shapiro–Wilk normality test of residuals | 0.1229 | 0.4518 |
Name | Mass 1 (mg) ± SD | Diameter 1 (mm) ± SD | Force 2 (N) ± SD |
---|---|---|---|
TP_100/200 | 442.61 ± 41.60 | 10.81 ± 5.47 | 8.40 ± 0.79 |
TP_50/100 | 369.77 ± 49.98 | 9.90 ± 0.70 | 9.29 ± 0.73 |
TP_50/100′ | Printing failed | ||
TP_AscA1_100/200 | Printing failed | ||
TP_AscA2_100/200 | |||
TP_AscA3_100/200 | |||
TP_TRI_100/200 | 760.06 ± 103.19 | 12.08 ± 0.51 | 4.93 ± 3.43 |
TP_TRI_50/50 | 563.53 ± 55.58 537.62 ± 19.30 * | 11.55 ± 0.64 11.26 ± 0.37 * | 5.93 ± 0.57 * |
TP_TRI_50/25 | 490.49 ± 28.50 477.15 ± 18.78 * | 10.45 ± 0.23 10.38 ± 0.13 * | 6.52 ± 0.26 * |
TP_TRI_50/25′ | 487.67 ± 27.56 476.09 ± 17.88 * | 10.32 ± 0.20 10.23 ± 0.08 * | 6.28 ± 0.75 * |
TP_TRI_50/12.5 | Printing failed |
Name of Tablets | Mass 1 (mg) ± SD | Diameter 1 (mm) ± SD | Force 2 (N) ± SD | Drug-Loading 3 (%) ± SD | Dosage (mg) |
---|---|---|---|---|---|
TMEB_50/25 | 388.39 ± 13.71 | 9.78 ± 0.17 | 6.44 ± 0.66 | 10.83 ± 0.32 | 41.94 |
TMEB_50/25′ | 384.06 ± 17.41 * | 9.41 ± 0.30 * | - | - | - |
TMEB_50/50 | 423.66 ± 9.96 | 10.12 ± 0.19 | 7.73 ± 0.53 | 11.21 ± 0.02 | 47.73 |
TMEB_50/50′ | 426.66 ± 5.79 | 10.02 ± 0.11 | 7.60 ± 0.26 | 11.00 ± 0.17 | 47.23 |
Project | 3D Printed Tablets | ||||
---|---|---|---|---|---|
Diameter (mm) | Height (mm) | Volume (mm3) | Diameter (mm) ± RSD (%) | Height (mm) ± RSD (%) | Mass (mg) ± RSD (%) |
14 | 7 | 1070.66 | 14.01 ± 0.51 | 6.72 ± 0.43 | 1194.70 ± 1.59 |
12 | 6 | 674.23 | 12.01 ± 0.34 | 5.72 ± 0.49 | 766.16 ± 2.00 |
10 | 5 | 390.18 | 10.13 ± 0.05 | 4.80 ± 0.77 | 464.35 ± 3.59 |
8 | 4 | 199.77 | 8.03 ± 0.20 | 3.77 ± 0.87 | 234.54 ± 5.31 |
6 | 3 | 84.28 | 5.94 ± 0.95 | 2.77 ± 1.68 | 94.66 ± 7.56 |
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Pyteraf, J.; Pacławski, A.; Jamróz, W.; Mendyk, A.; Paluch, M.; Jachowicz, R. Application and Multi-Stage Optimization of Daylight Polymer 3D Printing of Personalized Medicine Products. Pharmaceutics 2022, 14, 843. https://doi.org/10.3390/pharmaceutics14040843
Pyteraf J, Pacławski A, Jamróz W, Mendyk A, Paluch M, Jachowicz R. Application and Multi-Stage Optimization of Daylight Polymer 3D Printing of Personalized Medicine Products. Pharmaceutics. 2022; 14(4):843. https://doi.org/10.3390/pharmaceutics14040843
Chicago/Turabian StylePyteraf, Jolanta, Adam Pacławski, Witold Jamróz, Aleksander Mendyk, Marian Paluch, and Renata Jachowicz. 2022. "Application and Multi-Stage Optimization of Daylight Polymer 3D Printing of Personalized Medicine Products" Pharmaceutics 14, no. 4: 843. https://doi.org/10.3390/pharmaceutics14040843
APA StylePyteraf, J., Pacławski, A., Jamróz, W., Mendyk, A., Paluch, M., & Jachowicz, R. (2022). Application and Multi-Stage Optimization of Daylight Polymer 3D Printing of Personalized Medicine Products. Pharmaceutics, 14(4), 843. https://doi.org/10.3390/pharmaceutics14040843