Development of a Biphasic-Release Multiple-Unit Pellet System with Diclofenac Sodium Using Novel Calcium Phosphate-Based Starter Pellets
Abstract
:1. Introduction
2. Materials and Methods
2.1. Preparation of Multiple-Unit Diclofenac Sodium Capsules
2.2. Characterization of Starter and Drug-Layered Pellets
2.3. Scanning Electron Microscopy and Raman Imaging
2.4. Dissolution Tests (Modified Compendial Methods)
2.5. Dissolution under Conditions Simulating pH Changes in Fasted and Fed States
- (A)
- Simulation of fasted state:
- 120 min in 0.1 M hydrochloric acid pH 1.0 at 15 dpm;
- 20 min in 0.05 M phosphate buffer solution pH 5.6 at 15 dpm;
- 100 min in 0.05 M phosphate buffer solution pH 6.8 at 15 dpm;
- 1080 min in 0.05 M phosphate buffer solution pH 6.8 at 10 dpm;
- (B)
- Simulation of fed state:
- 30 min in 0.05 M phosphate buffer solution pH 4.5 at 8 dpm;
- 60 min in 0.05 M phosphate buffer solution pH 3.5 at 8 dpm;
- 150 min in 0.01 M hydrochloric acid pH 2.0 at 15 dpm;
- 30 min in 0.05 M phosphate buffer solution pH 5.6 at 15 dpm;
- 330 min in 0.05 M phosphate buffer solution pH 6.8 at 15 dpm;
- 840 min in 0.05 M phosphate buffer solution pH 6.8 at 10 dpm.
3. Results
3.1. Characterization of Starter and Drug-Layered Pellets
3.2. Dissolution Testing of Diclofenac Sodium DR Pellets
3.3. Dissolution Test of Diclofenac Sodium XR Pellets
3.4. Dissolution Test of Diclofenac Sodium 75 mg BPR Hard Gelatin Capsules (Modified Compendial Methods)
3.5. Dissolution under Conditions Simulating pH Changes in Fasted and Fed States
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Process Parameter | Drug Loading | Enteric Release Coating | Functional Film Coating |
---|---|---|---|
Inlet airflow rate | 0.31 ± 0.1 m3/min | 0.32 ± 0.1 m3/min | 0.30 ± 0.1 m3/min |
Inlet air temperature | 57 ± 2 °C | 56 ± 2 °C | 31 ± 2 °C |
Product temperature | 40 ± 2 °C | 41 ± 2 °C | 26 ± 2 °C |
Spraying pressure | 1.1 ± 0.2 bar | 1.1 ± 0.2 bar | 1.0 ± 0.2 bar |
Coating mixture flow rate | 1.3 g/min | 1.0 g/min | 1.0 g/min |
Drying time | 10 min | 30 min | 30 min |
Curing time and temperature | - | - | 24 h at 42 ± 2 °C |
Inert Cores | DCPA Pellets | MCC Spheres | Sugar Spheres | Isomalt Pellets |
---|---|---|---|---|
Starter pellets | 1.06 ± 0.02 g/mL | 0.89 ± 0.01 g/mL | 0.87 ± 0.01 g/mL | 0.81 ± 0.02 g/mL |
DR drug-loaded pellets | 1.02 ± 0.01 g/mL | 0.85 ± 0.02 g/mL | 0.88 ± 0.01 g/mL | 0.86 ± 0.02 g/mL |
XR drug-loaded pellets | 1.05 ± 0.02 g/mL | 0.92 ± 0.02 g/mL | 0.89 ± 0.02 g/mL | 0.90 ± 0.02 g/mL |
Inert Cores | DCPA Pellets | MCC Spheres | Sugar Spheres | Isomalt Pellets | ||||
---|---|---|---|---|---|---|---|---|
Parameter | Roundness | Convexity | Roundness | Convexity | Roundness | Convexity | Roundness | Convexity |
Starter pellets | 0.891 ± 0.015 | 0.995 ± 0.004 | 0.874 ± 0.023 | 0.993 ± 0.007 | 0.845 ± 0.030 | 0.981 ± 0.011 | 0.787 ± 0.042 | 0.968 ± 0.013 |
DR drug-loaded pellets | 0.892 ± 0.017 | 0.998 ± 0.005 | 0.869 ± 0.028 | 0.994 ± 0.008 | 0.845 ± 0.057 | 0.978 ± 0.027 | 0.785 ± 0.082 | 0.956 ± 0.047 |
XR drug-loaded pellets | 0.890 ± 0.022 | 0.993 ± 0.010 | 0.873 ± 0.026 | 0.991 ± 0.012 | 0.867 ± 0.034 | 0.991 ± 0.014 | 0.828 ± 0.034 | 0.985 ± 0.010 |
Inert Cores | DCPA Pellets | MCC Spheres | Sugar Spheres | Isomalt Pellets |
---|---|---|---|---|
DR drug-loaded pellets | 7.37 ± 0.01% | 7.62 ± 0.04% | 7.31 ± 0.07% | 7.24 ± 0.05% |
XR drug-loaded pellets | 8.02 ± 0.06% | 8.04 ± 0.08% | 7.93 ± 0.01% | 8.18 ± 0.09% |
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Zakowiecki, D.; Frankiewicz, M.; Hess, T.; Cal, K.; Gajda, M.; Dabrowska, J.; Kubiak, B.; Paszkowska, J.; Wiater, M.; Hoc, D.; et al. Development of a Biphasic-Release Multiple-Unit Pellet System with Diclofenac Sodium Using Novel Calcium Phosphate-Based Starter Pellets. Pharmaceutics 2021, 13, 805. https://doi.org/10.3390/pharmaceutics13060805
Zakowiecki D, Frankiewicz M, Hess T, Cal K, Gajda M, Dabrowska J, Kubiak B, Paszkowska J, Wiater M, Hoc D, et al. Development of a Biphasic-Release Multiple-Unit Pellet System with Diclofenac Sodium Using Novel Calcium Phosphate-Based Starter Pellets. Pharmaceutics. 2021; 13(6):805. https://doi.org/10.3390/pharmaceutics13060805
Chicago/Turabian StyleZakowiecki, Daniel, Maja Frankiewicz, Tobias Hess, Krzysztof Cal, Maciej Gajda, Justyna Dabrowska, Bartlomiej Kubiak, Jadwiga Paszkowska, Marcela Wiater, Dagmara Hoc, and et al. 2021. "Development of a Biphasic-Release Multiple-Unit Pellet System with Diclofenac Sodium Using Novel Calcium Phosphate-Based Starter Pellets" Pharmaceutics 13, no. 6: 805. https://doi.org/10.3390/pharmaceutics13060805
APA StyleZakowiecki, D., Frankiewicz, M., Hess, T., Cal, K., Gajda, M., Dabrowska, J., Kubiak, B., Paszkowska, J., Wiater, M., Hoc, D., Garbacz, G., & Haznar-Garbacz, D. (2021). Development of a Biphasic-Release Multiple-Unit Pellet System with Diclofenac Sodium Using Novel Calcium Phosphate-Based Starter Pellets. Pharmaceutics, 13(6), 805. https://doi.org/10.3390/pharmaceutics13060805