Predicting Drug Release from 3D Printed Oral Medicines Based on the Surface Area to Volume Ratio of Tablet Geometry
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials
2.2. Methods
2.2.1. Hot Melt Extrusion
2.2.2. 3D Printing of Tablets
2.2.3. Dissolution Test
2.2.4. Mathematical Description
Release Modeling
Prediction
Comparison of the Dissolution Profiles
2.2.5. Characterization of the Printed Tablets
3. Results
3.1. Characterization of the Printed Tablets
3.2. Drug Release from Dosage Forms with Defined SA/V Ratios
3.3. Correlation between MDT and SA/V Ratio
3.4. Modeling and Prediction of Release Profiles
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Acknowledgments
Conflicts of Interest
References
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Temperature Profile in Zone 2–10/°C | |||||||||
---|---|---|---|---|---|---|---|---|---|
Zone/- | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 |
PVA-PDM formulation/°C | 30 | 100 | 180 | 180 | 180 | 180 | 180 | 195 | 195 |
PVA-PZQ formulation/°C | 21 | 31 | 78 | 180 | 180 | 180 | 180 | 180 | 190 |
EVA-LD formulation/°C | 25 | 28 | 78 | 130 | 140 | 155 | 155 | 120 | 100 |
Screw Configuration (Die–Gear) | |||||||||
PVA/EVA formulation | die-10 CE 1 L/D-KZ: 5 × 60°-3 × 30°-5 CE 1 L/D-KZ: 4 × 90°-5 × 60°-3 × 30°-10 CE 1 L/D-2 CE 3/2 L/D-gear | ||||||||
CE = conveying element, KZ = kneading zone |
n | |||
---|---|---|---|
Thin Film | Cylinder | Sphere | Drug Release Mechanism |
0.50 | 0.45 | 0.43 | Fickian diffusion |
0.50 < n < 1.00 | 0.45 < n < 0.89 | 0.43 < n < 0.85 | Anomalous transport |
1.00 | 0.89 | 0.85 | Case-II transport |
SA/V 1 mm−1 | ||||||
---|---|---|---|---|---|---|
Form | SA/mm2 | V/mm3 | SA/V/mm−1 | API/mg | MDT/min | f2 Value |
Q1 | 606.00 | 585.00 | 1.00 | 35.97 | 56.95 | 77.51 |
Q2 | 256.00 | 256.00 | 1.00 | 15.60 | 62.91 | 87.92 |
Q3 | 250.00 | 250.00 | 1.00 | 15.66 | 65.65 | 73.88 |
HC | 667.59 | 667.59 | 1.00 | 41.34 | 56.84 | 71.87 |
C | 201.06 | 201.06 | 1.00 | 12.29 | 60.67 | Reference |
P | 273.05 | 265.97 | 1.03 | 16.25 | 64.30 | 82.89 |
SA/V 1.5 mm−1 | ||||||
Form | SA/mm2 | V/mm3 | SA/V/mm−1 | API/mg | MDT/min | f2 Value |
Q1 | 546.00 | 360.00 | 1.52 | 21.74 | 32.81 | 78.20 |
Q2 | 192.00 | 128.00 | 1.50 | 8.00 | 35.67 | 92.54 |
Q3 | 166.00 | 110.00 | 1.51 | 6.92 | 38.07 | 73.19 |
HC | 301.59 | 201.06 | 1.50 | 13.54 | 33.83 | 90.82 |
C | 150.80 | 100.53 | 1.50 | 6.19 | 34.80 | Reference |
P | 121.92 | 80.10 | 1.52 | 4.85 | 36.92 | 75.40 |
SA/V 2 mm−1 | ||||||
Form | SA/mm2 | V/mm3 | SA/V/mm−1 | API/mg | MDT/min | f2 Value |
Q1 | 516.00 | 247.50 | 2.08 | 15.04 | 22.98 | 66.45 |
Q2 | 169.60 | 83.20 | 2.04 | 5.21 | 25.70 | 96.55 |
Q3 | 142.00 | 70.00 | 2.03 | 4.43 | 24.90 | 91.95 |
HC | 201.06 | 100.50 | 2.00 | 6.87 | 25.02 | 92.37 |
C | 133.20 | 65.35 | 2.04 | 3.92 | 25.14 | Reference |
P | 66.02 | 32.24 | 2.05 | 1.99 | 24.86 | 75.79 |
SA/V Ratio/mm−1 | MDT Prediction/min | MDT Experiment/min | RMSEP/min |
---|---|---|---|
0.90 | 71.70 | 74.06 ± 11.45 | 2.36 |
1.60 | 33.83 | 31.04 ± 2.20 | 2.79 |
2.30 | 21.07 | 16.65 ± 0.46 | 4.42 |
4.67 | 8.36 | 6.93 ± 0.71 | 1.43 |
SA/V Ratio/mm−1 | MDT Prediction/min | MDT Experiment/min | RMSEP/min |
---|---|---|---|
1.73 | 82.25 | 78.79 ± 7.24 | 3.46 |
1.89 | 70.74 | 62.60 ± 5.90 | 8.14 |
4.67 | 15.13 | 14.40 ± 0.77 | 0.73 |
SA/V Ratio/mm−1 | MDT Prediction/min | MDT Experiment/min | RMSEP/min |
---|---|---|---|
1.30 | 54.42 | 55.91 ± 1.11 | 1.49 |
1.83 | 36.79 | 38.73 ± 1.07 | 1.94 |
2.30 | 28.32 | 27.88 ± 2.23 | 0.44 |
4.67 | 12.58 | 12.16 ± 0.96 | 0.42 |
PVA-PDM Formulation | ||||||
---|---|---|---|---|---|---|
SA/V mm−1 | KMP | Hixson | Peppas Sahlin n = 0.79 | Hopfenberg | Lapidus + Lordi | Weibull |
0.8 | 0.9837 | 0.9951 | 0.9991 | 0.9837 | 0.9837 | 0.1240 |
1.0 | 0.9971 | 0.9969 | 0.9989 | 0.9971 | 0.9971 | 0.1620 |
1.5 | 0.9981 | 0.9964 | 0.9995 | 0.9981 | 0.9981 | 0.2575 |
2.0 | 0.9966 | 0.9961 | 0.9996 | 0.9966 | 0.9966 | 0.9919 |
2.5 | 0.9783 | 0.9975 | 0.9978 | 0.9783 | 0.9783 | 0.9957 |
3.3 | 0.9982 | 0.9951 | 0.9997 | 0.9982 | 0.9982 | 0.9955 |
4.0 | 0.9949 | 0.9964 | 0.9995 | 0.9949 | 0.9949 | 0.9971 |
5.0 | 0.9931 | 0.9987 | 0.9999 | 0.9931 | 0.9931 | 0.9994 |
6.0 | 0.9970 | 0.9987 | 0.9999 | 0.9970 | 0.9970 | 0.9997 |
PVA-PZQ Formulation | ||||||
SA/V mm−1 | KMP | Hixson | Peppas Sahlin n= 1.1 | Hopfenberg | Lapidus + Lordi | Weibull |
0.8 | 0.9680 | 0.9922 | 0.9980 | 0.9680 | 0.9680 | 0.9993 |
1.0 | 0.9870 | 0.9832 | 0.9953 | 0.9870 | 0.9870 | 0.9972 |
1.5 | 0.9765 | 0.9727 | 0.9890 | 0.9765 | 0.9765 | 0.9976 |
2.0 | 0.9663 | 0.9646 | 0.9667 | 0.9663 | 0.9663 | 0.9973 |
2.5 | 0.9819 | 0.9292 | 0.9932 | 0.9819 | 0.9819 | 0.9963 |
3.3 | 0.9350 | 0.9408 | 0.9807 | 0.9350 | 0.9350 | 0.9980 |
4.0 | 0.9331 | 0.9361 | 0.9877 | 0.9331 | 0.9331 | 0.9975 |
5.0 | 0.9143 | 0.9787 | 0.9823 | 0.9143 | 0.9143 | 0.9994 |
6.0 | 0.9429 | 0.9299 | 0.9888 | 0.9429 | 0.9429 | 0.9992 |
EVA-LD Formulation | ||||||
SA/V mm−1 | KMP | Weibull | Peppas Sahlin n= 0.66 | Higuchi | ||
0.9 | 0.9941 | 0.9986 | 0.9808 | 0.8760 | ||
1.1 | 0.9910 | 0.9936 | 0.9853 | 0.9304 | ||
1.5 | 0.9961 | 0.9961 | 0.9981 | 0.9945 | ||
1.7 | 0.9925 | 0.9884 | 0.9966 | 0.9880 | ||
1.9 | 0.9949 | 0.9894 | 0.9989 | 0.9941 | ||
2.5 | 0.9724 | 0.9979 | 0.9993 | 0.9282 | ||
4.0 | 0.9979 | 0.9928 | 0.9934 | 0.9730 | ||
5.0 | 0.9970 | 0.9944 | 0.9956 | 0.9583 | ||
6.0 | 0.9974 | 0.9946 | 0.9957 | 0.9600 |
PVA−PDM Formulation | |||||
---|---|---|---|---|---|
SA/V | k1 | k2 | ln(SA/V) | ln(k1) | ln(k2) |
0.8 | 1.986 | 0.010 | −0.223 | 0.686 | −4.608 |
1.0 | 2.516 | 0.011 | 0.000 | 0.923 | −4.549 |
1.5 | 3.920 | 0.027 | 0.405 | 1.366 | −3.626 |
2.0 | 5.561 | 0.067 | 0.693 | 1.716 | −2.704 |
2.5 | 7.362 | 0.135 | 0.916 | 1.996 | −2.001 |
3.3 | 11.555 | 0.258 | 1.203 | 2.447 | −1.353 |
4.0 | 15.459 | 0.545 | 1.386 | 2.738 | −0.608 |
5.0 | 16.888 | 0.713 | 1.609 | 2.827 | −0.338 |
6.0 | 20.856 | 1.069 | 1.792 | 3.038 | 0.066 |
EVA−LD Formulation | |||||
SA/V | k1 | k2 | ln(SA/V) | ln(k1) | ln(k2) |
0.9 | 1.952 | 0.010 | −0.105 | 0.669 | −4.614 |
1.1 | 2.286 | 0.014 | 0.065 | 0.827 | −4.282 |
1.5 | 3.115 | 0.020 | 0.405 | 1.136 | −3.928 |
1.7 | 4.087 | 0.031 | 0.513 | 1.408 | −3.465 |
1.9 | 5.009 | 0.053 | 0.626 | 1.611 | −2.944 |
2.5 | 7.636 | 0.153 | 0.916 | 2.033 | −1.876 |
4.0 | 10.374 | 0.279 | 1.386 | 2.339 | −1.277 |
5.0 | 14.444 | 0.540 | 1.609 | 2.670 | −0.617 |
6.0 | 16.816 | 0.727 | 1.792 | 2.822 | −0.319 |
PVA-PZQ Formulation | |||||
---|---|---|---|---|---|
SA/V | a | b | ln(SA/V) | ln(a) | ln(b) |
0.8 | 105.0 | 1.38 | −0.223 | 4.654 | 0.322 |
1.0 | 81.0 | 1.45 | 0.000 | 4.394 | 0.372 |
1.5 | 52.0 | 1.63 | 0.405 | 3.951 | 0.489 |
2.0 | 38.0 | 1.80 | 0.693 | 3.638 | 0.588 |
2.5 | 31.5 | 1.91 | 0.916 | 3.450 | 0.647 |
3.3 | 20.8 | 2.05 | 1.194 | 3.035 | 0.718 |
4.0 | 17.1 | 2.15 | 1.386 | 2.836 | 0.765 |
5.0 | 11.5 | 2.29 | 1.609 | 2.442 | 0.829 |
6.0 | 11.2 | 2.40 | 1.792 | 2.414 | 0.875 |
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Windolf, H.; Chamberlain, R.; Quodbach, J. Predicting Drug Release from 3D Printed Oral Medicines Based on the Surface Area to Volume Ratio of Tablet Geometry. Pharmaceutics 2021, 13, 1453. https://doi.org/10.3390/pharmaceutics13091453
Windolf H, Chamberlain R, Quodbach J. Predicting Drug Release from 3D Printed Oral Medicines Based on the Surface Area to Volume Ratio of Tablet Geometry. Pharmaceutics. 2021; 13(9):1453. https://doi.org/10.3390/pharmaceutics13091453
Chicago/Turabian StyleWindolf, Hellen, Rebecca Chamberlain, and Julian Quodbach. 2021. "Predicting Drug Release from 3D Printed Oral Medicines Based on the Surface Area to Volume Ratio of Tablet Geometry" Pharmaceutics 13, no. 9: 1453. https://doi.org/10.3390/pharmaceutics13091453
APA StyleWindolf, H., Chamberlain, R., & Quodbach, J. (2021). Predicting Drug Release from 3D Printed Oral Medicines Based on the Surface Area to Volume Ratio of Tablet Geometry. Pharmaceutics, 13(9), 1453. https://doi.org/10.3390/pharmaceutics13091453