Dose Titration of Solid Dosage Forms via FDM 3D-Printed Mini-Tablets
Abstract
:1. Introduction
- Single and multi-unit mini-tablets, i.e., 1, 5, 10, 15, 20 count(s), to test content uniformity at a low dose, i.e., 1 wt%, and to evaluate corresponding dissolution profiles to assess their similarity.
- Split tablets, i.e., full, half, and quarter sizes, to compare with multi-unit mini-tablets along with testing content uniformity and dissolution.
- Single unit mini-tablets formed using filaments of 10 and 20 wt% drug concentrations for testing feasibility of reducing the number of tablets to be administered.
2. Materials and Methods
2.1. Materials
2.2. Manufacturing of Filaments
2.3. FDM 3D Printing and Tablet Morphology
2.4. Thermo-Gravimetric Analysis (TGA)
2.5. Solid-State Characterization
2.6. Content Uniformity
2.7. Dissolution
3. Results
3.1. Mini-Tablet Printing and Tablet Morphology
3.2. Thermo-Gravimetric Analysis (TGA)
3.3. X-ray Diffraction (XRD)
3.4. Content Uniformity and Dose Titration
3.4.1. Content Uniformity
3.4.2. Dose Titration
3.5. Drug Dissolution
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Run | Formulation | HME Processing Temperature (°C) | HME Screw Speed (rpm) |
---|---|---|---|
F1 | 1 wt% GF + 84 wt% HPC + 15 wt% KP | 150 | 40 |
F10 | 10 wt% GF + 75 wt% HPC + 15 wt% KP | 150 | 40 |
F20 | 20 wt% GF + 65 wt% HPC + 15 wt% KP | 155 | 40 |
Run | Theoretical Drug Concentration (wt%) | Radius * (mm) | Height * (mm) | Number of Unit(s) | |
---|---|---|---|---|---|
M1 | 1% (F1) | 1.5 | 2 | 1 | |
M2 | 1.5 | 2 | 5 | ||
M3 | 1.5 | 2 | 10 | ||
M4 | 1.5 | 2 | 15 | ||
M5 | 1.5 | 2 | 20 | ||
M6 | 10% (F10) | 1.5 | 2 | 1 | |
M7 | 20% (F20) | 1.5 | 2 | 1 | |
F | 6.5 | 2.2 | 1 | ||
H | 1% (F1) | 6.5 | 2.2 | 1 | |
Q | 6.5 | 2.2 | 1 |
Run | DC 1 (wt%) | Number of Tablet Unit(s) | Tablet Mass (mg) | Drug Mass (mg) | RSD | LC% 2 | AV 3 |
---|---|---|---|---|---|---|---|
M1 | 1 | 1 | 19.18 ± 0.32 | 0.19 ± 0.01 | 4.57 | 99.67 ± 3.92 | 7.83 |
M2 | 1 | 5 | 97.97 ± 1.95 | 1.04 ± 0.03 | 2.62 | 105.96 ± 0.84 | 0.44 |
M3 | 1 | 10 | 191.53 ± 1.12 | 1.93 ± 0.01 | 0.77 | 100.79 ± 0.22 | 1.78 |
M4 | 1 | 15 | 279.77 ± 3.84 | 2.85 ± 0.06 | 2.01 | 101.97 ± 0.66 | 2.39 |
M5 | 1 | 20 | 379.13 ± 2.15 | 3.91 ± 0.02 | 0.60 | 103.17 ± 0.36 | 6.49 |
F | 1 | 1 | 312.23 ± 11.11 | 2.93 ± 0.07 | 2.44 | 93.92 ± 1.04 | 6.67 |
H | 1 | 0.5 | 201.97 ± 2.73 | 1.95 ± 0.02 | 0.97 | 96.73 ± 0.50 | 2.77 |
Q | 1 | 0.25 | 104.63 ± 0.73 | 1.00 ± 0.00 | 0.33 | 95.92 ± 0.08 | 2.75 |
M6 | 10 | 1 | 20.03 ± 0.39 | 1.95 ± 0.04 | 1.90 | 97.25 ± 0.52 | 2.30 |
M7 | 20 | 1 | 19.60 ± 0.32 | 3.76 ± 0.06 | 1.61 | 96.00 ± 0.35 | 3.19 |
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Gorkem Buyukgoz, G.; Kossor, C.G.; Ji, S.; Guvendiren, M.; Davé, R.N. Dose Titration of Solid Dosage Forms via FDM 3D-Printed Mini-Tablets. Pharmaceutics 2022, 14, 2305. https://doi.org/10.3390/pharmaceutics14112305
Gorkem Buyukgoz G, Kossor CG, Ji S, Guvendiren M, Davé RN. Dose Titration of Solid Dosage Forms via FDM 3D-Printed Mini-Tablets. Pharmaceutics. 2022; 14(11):2305. https://doi.org/10.3390/pharmaceutics14112305
Chicago/Turabian StyleGorkem Buyukgoz, Guluzar, Christopher G. Kossor, Shen Ji, Murat Guvendiren, and Rajesh N. Davé. 2022. "Dose Titration of Solid Dosage Forms via FDM 3D-Printed Mini-Tablets" Pharmaceutics 14, no. 11: 2305. https://doi.org/10.3390/pharmaceutics14112305