Co-Amorphous Formation of Simvastatin-Ezetimibe: Enhanced Physical Stability, Bioavailability and Cholesterol-Lowering Effects in LDLr−/−Mice
Abstract
:1. Introduction
2. Methods
2.1. Materials
2.2. Preparation of SIM-EZE PM and SIM-EZE CO
2.3. Characterization of CO
2.3.1. Thermogravimetric Analysis (TGA)
2.3.2. Differential Scanning Calorimetry (DSC)
2.3.3. Fourier Transform Infrared Spectroscopy (FT-IR)
2.3.4. Physical Stability
2.3.5. In Vitro Powder Dissolution
2.3.6. HPLC
2.3.7. Gordon–Taylor Equation for Theoretical Tg Calculation
2.4. In Vivo Pharmacokinetic Study
2.5. Pharmacodynamic Study on the Hypolipidemic Effects of the CO
2.6. Plasma TC and TG Measurement
2.7. Determination of Cholesterol in the Mouse Feces
2.8. RNA Extraction and q-PCR Analysis
2.9. Statistical Analysis
3. Results
3.1. Characterization of SIM-EZE CO
3.1.1. Thermal Analysis
3.1.2. FT-IR Spectroscopy
3.1.3. Physical Stability
3.1.4. In Vitro Powder Dissolution
3.2. Pharmacokinetic Study
3.3. Dose-Dependent Cholesterol-Lowering Effects of the SIM-EZE PM
3.4. Pharmacodynamics Studies of the SIM-EZE CO and PM
3.5. Determination of Cholesterol Content in Mouse Feces and Effects of EZE on the mRNA Level of NPC1L1 in the Mouse Intestines
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Acknowledgments
Conflicts of Interest
References
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PK Parameters | CO | PM |
---|---|---|
Cmax/μg·mL−1 | 131.346 ± 0.88 | 91.141 ± 11.062 *** |
Tmax/h | 2.00 ± 0 | 2.00 ± 0 |
t1/2/h | 1.7167 ± 0.098 | 1.7439 ± 0.09 |
AUC(0–t)/μg·mL−1·h | 728.33 ± 93.30 | 605.26 ± 24.76 * |
AUC(0–∞)/μg·mL−1·h | 781.23 ± 94.07 | 605.52 ± 24.77 ** |
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Bahetibieke, S.; Moinuddin, S.M.; Baiyisaiti, A.; Liu, X.; Zhang, J.; Liu, G.; Shi, Q.; Peng, A.; Tao, J.; Di, C.; et al. Co-Amorphous Formation of Simvastatin-Ezetimibe: Enhanced Physical Stability, Bioavailability and Cholesterol-Lowering Effects in LDLr−/−Mice. Pharmaceutics 2022, 14, 1258. https://doi.org/10.3390/pharmaceutics14061258
Bahetibieke S, Moinuddin SM, Baiyisaiti A, Liu X, Zhang J, Liu G, Shi Q, Peng A, Tao J, Di C, et al. Co-Amorphous Formation of Simvastatin-Ezetimibe: Enhanced Physical Stability, Bioavailability and Cholesterol-Lowering Effects in LDLr−/−Mice. Pharmaceutics. 2022; 14(6):1258. https://doi.org/10.3390/pharmaceutics14061258
Chicago/Turabian StyleBahetibieke, Shamuha, Sakib M. Moinuddin, Asiya Baiyisaiti, Xiaoang Liu, Jie Zhang, Guomin Liu, Qin Shi, Ankang Peng, Jun Tao, Chang Di, and et al. 2022. "Co-Amorphous Formation of Simvastatin-Ezetimibe: Enhanced Physical Stability, Bioavailability and Cholesterol-Lowering Effects in LDLr−/−Mice" Pharmaceutics 14, no. 6: 1258. https://doi.org/10.3390/pharmaceutics14061258
APA StyleBahetibieke, S., Moinuddin, S. M., Baiyisaiti, A., Liu, X., Zhang, J., Liu, G., Shi, Q., Peng, A., Tao, J., Di, C., Cai, T., & Qi, R. (2022). Co-Amorphous Formation of Simvastatin-Ezetimibe: Enhanced Physical Stability, Bioavailability and Cholesterol-Lowering Effects in LDLr−/−Mice. Pharmaceutics, 14(6), 1258. https://doi.org/10.3390/pharmaceutics14061258