Revisiting Supersaturation of a Biopharmaceutical Classification System IIB Drug: Evaluation via a Multi-Cup Dissolution Approach and Molecular Dynamic Simulation
Abstract
:1. Introduction
2. Results and Discussions
2.1. pH-Dependent Solubility
2.2. In Vitro Supersaturation–Precipitation and Absorption Assay
2.2.1. Supersaturation–Precipitation and Absorption in the DGIM
2.2.2. Supersaturation and Absorption in the USP II
2.3. Solid State Characterizations
2.4. Molecular Dynamic Simulation
2.5. In Vivo Pharmacokinetics
2.6. IVIVC
3. Materials and Methods
3.1. Materials
3.2. pH-Dependent Solubility Measurements
3.3. In Vitro Supersaturation–Precipitation and Absorption Assay
3.3.1. Supersaturation–Precipitation and Absorption in the DGIM
3.3.2. Supersaturation–Precipitation and Absorption in the USP II
3.4. Solid State Characterizations
3.4.1. Polarizing Microscopy
3.4.2. Scanning Electron Microscopy
3.4.3. X-ray Powder Diffraction
3.4.4. Differential Scanning Calorimetry
3.5. Molecular Dynamic Simulation
3.6. Pharmacokinetic Study
3.7. In Vitro–In Vivo Correlation
3.8. Statistics
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Data Availability Statement
Conflicts of Interest
Sample Availability
References
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Group | Duodenal | Jejunal | ||
---|---|---|---|---|
DSmax | DSAUC | DSmax | DSAUC | |
Control | 8.837 | 3.715 | 9.643 | 5.452 |
PVPVA | 10.68 | 6.988 | 13.53 | 6.859 |
HPMC | 8.507 | 6.095 | 15.05 | 6.660 |
DGIM | USP II | ||||||||
---|---|---|---|---|---|---|---|---|---|
Control | PVPVA | HPMC | Mean | Control | PVPVA | HPMC | Mean | ||
Cmax (ng·mL−1) | Observation | 41,300 | 48,100 | 45,400 | 41,300 | 48,100 | 45,400 | ||
Prediction | 45,529 | 54,269 | 48,488 | 45,702 | 58,480 | 57,044 | |||
PE (%) | 10.24 | 12.83 | 6.80 | 9.96 | 10.66 | 21.58 | 25.65 | 19.3 | |
AUC (h·ng·mL−1) | Observation | 112,853 | 146,143 | 135,015 | 112,853 | 146,144 | 135,015 | ||
Prediction | 114,652 | 144,456 | 135,032 | 108,727 | 149,731 | 126,032 | |||
PE (%) | 1.59 | −1.16 | 0.01 | 0.92 | −3.66 | 2.45 | −6.65 | 4.25 |
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Gan, Y.; Xu, Y.; Zhang, X.; Hu, H.; Xiao, W.; Yu, Z.; Sun, T.; Zhang, J.; Wen, C.; Zheng, S. Revisiting Supersaturation of a Biopharmaceutical Classification System IIB Drug: Evaluation via a Multi-Cup Dissolution Approach and Molecular Dynamic Simulation. Molecules 2023, 28, 6962. https://doi.org/10.3390/molecules28196962
Gan Y, Xu Y, Zhang X, Hu H, Xiao W, Yu Z, Sun T, Zhang J, Wen C, Zheng S. Revisiting Supersaturation of a Biopharmaceutical Classification System IIB Drug: Evaluation via a Multi-Cup Dissolution Approach and Molecular Dynamic Simulation. Molecules. 2023; 28(19):6962. https://doi.org/10.3390/molecules28196962
Chicago/Turabian StyleGan, Yanxiong, Yaxin Xu, Xue Zhang, Huiling Hu, Wenke Xiao, Zheng Yu, Tao Sun, Jinming Zhang, Chuanbiao Wen, and Shichao Zheng. 2023. "Revisiting Supersaturation of a Biopharmaceutical Classification System IIB Drug: Evaluation via a Multi-Cup Dissolution Approach and Molecular Dynamic Simulation" Molecules 28, no. 19: 6962. https://doi.org/10.3390/molecules28196962