Cyclodextrin Complexation as a Way of Increasing the Aqueous Solubility and Stability of Carvedilol
Abstract
:1. Introduction
2. Materials and Methods
2.1. Chemicals
2.2. Ultra High Performance Liquid Chromatography
2.3. Solubility Studies
2.4. Nuclear Magnetic Resonance (NMR) Analyses
2.5. Aggregation Studies
2.6. Complex Stoichiometry
2.7. Isothermal Titration Calorimetry (ITC) Studies
2.8. Mass Spectrometry Studies
2.9. UV Studies
2.10. Photostability Study
3. Results and Discussion
3.1. Solubility Studies
3.2. Aggregation Studies
3.3. Complexation Studies
3.3.1. NMR Studies
3.3.2. ITC Studies
3.4. Photostability Studies
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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Pure Water | 0.1 M Acetate Buffer | 0.1 M Citrate Buffer | 13 mM HCl | |||||
---|---|---|---|---|---|---|---|---|
S (mM) | R | S (mM) | R | S (mM) | R | S (mM) | R | |
No CD | 0.039 | - | 2.694 | - | 0.350 | - | 1.861 | - |
αCD | 0.044 | 1.14 | 3.501 | 1.30 | 0.450 | 1.29 | 2.157 | 1.16 |
βCD | 0.081 | 2.10 | 6.133 | 2.28 | 0.629 | 1.80 | 2.946 | 1.58 |
γCD | 0.092 | 2.38 | 12.881 | 4.78 | 0.901 | 2.58 | 3.242 | 1.74 |
HPβCD | 0.122 | 3.14 | 8.082 | 3.00 | 1.188 | 3.40 | 3.252 | 1.75 |
HPγCD | 0.128 | 3.30 | 13.734 | 5.10 | 0.910 | 2.60 | 3.527 | 1.89 |
RAMEB | 0.177 | 4.58 | 13.708 | 5.09 | 1.390 | 3.98 | 3.502 | 1.88 |
Carbazole | Methoxyphenyl | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
H1 | H3 | H5 | H6 | H11 | H12 | H13 | H28 | H26 | H24 | H25 | ||
βCD | H3 | ++ | +++ | ++ | +++ | - | ++ | + | ++ | ++ | ++ | ++ |
H5 | +++ | + | ++ | +++ | - | - | - | - | + | + | - | |
γCD | H3 | ++ | +++ | + | + | + | +++ | + | +++ | ++ | + | ND |
H5 | +++ | ++ | ++ | ++ | - | ND | - | ++ | ++ | ++ | +++ | |
DIMEB | H3 | ++ | +++ | ++ | ++ | + | ++ | + | ++ | ++ | +++ | +++ |
H5 | +++ | + | +++ | ++ | - | - | - | + | + | + | - | |
CH3(2) | + | - | - | - | ++ | ++ | ++ | - | + | + | - | |
CH3(6) | ++ | - | - | ++ | - | - | - | - | - | - | - |
Temperature (K) | K (M−1) | ΔH° (kJ·mol−1) | −TΔS° (J·mol−1·K−1) | ΔG° (kJ·mol−1) | |
---|---|---|---|---|---|
carvedilol/γCD | 288 | 296 ± 39 | −18.3 ± 0.4 | 4.7 ± 0.7 | −13.6 ± 0.3 |
298 | 225 ± 30 | −21.4 ± 0.5 | 8.4 ± 0.9 | −13.0 ± 0.3 | |
308 | 166 ± 22 | −24.4 ± 0.7 | 11.3 ± 1.1 | −13.1 ± 0.3 | |
carvedilol/RAMEB | 288 | 408 ± 60 | −17.7 ± 0.7 | 3.3 ± 1.0 | −14.4 ± 0.4 |
298 | 317 ± 47 | −18.0 ± 0.8 | 3.7 ± 1.2 | −14.3 ± 0.4 | |
308 | 250 ± 37 | −18.3 ± 0.9 | 4.1 ± 1.3 | −14.1 ± 0.4 |
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Rigaud, S.; Mathiron, D.; Moufawad, T.; Landy, D.; Djedaini-Pilard, F.; Marçon, F. Cyclodextrin Complexation as a Way of Increasing the Aqueous Solubility and Stability of Carvedilol. Pharmaceutics 2021, 13, 1746. https://doi.org/10.3390/pharmaceutics13111746
Rigaud S, Mathiron D, Moufawad T, Landy D, Djedaini-Pilard F, Marçon F. Cyclodextrin Complexation as a Way of Increasing the Aqueous Solubility and Stability of Carvedilol. Pharmaceutics. 2021; 13(11):1746. https://doi.org/10.3390/pharmaceutics13111746
Chicago/Turabian StyleRigaud, Sébastien, David Mathiron, Tarek Moufawad, David Landy, Florence Djedaini-Pilard, and Frédéric Marçon. 2021. "Cyclodextrin Complexation as a Way of Increasing the Aqueous Solubility and Stability of Carvedilol" Pharmaceutics 13, no. 11: 1746. https://doi.org/10.3390/pharmaceutics13111746
APA StyleRigaud, S., Mathiron, D., Moufawad, T., Landy, D., Djedaini-Pilard, F., & Marçon, F. (2021). Cyclodextrin Complexation as a Way of Increasing the Aqueous Solubility and Stability of Carvedilol. Pharmaceutics, 13(11), 1746. https://doi.org/10.3390/pharmaceutics13111746