Dasatinib/HP-β-CD Inclusion Complex Based Aqueous Formulation as a Promising Tool for the Treatment of Paediatric Neuromuscular Disorders
Abstract
:1. Introduction
2. Results and Discussion
2.1. Evaluation of the Inclusion Complex in Solution
2.2. Characterization of the Inclusion Complex in the Solid State
2.3. Dissolution Studies
2.4. Cytotoxicity Studies
2.5. Pharmacokinetic Results
3. Materials and Methods
3.1. Materials
3.2. Quantitative Analysis of DAS
3.3. Solubility and Phase-Solubility Studies
3.4. Preparation of Solid DAS /HP-β-CD Inclusion Complex
3.5. Determination of DAS Incorporation Degree in the Solid Cyclodextrin Inclusion Complex
3.6. Job’s Plot Method
3.7. 1H-NMR and Heteronuclear Multiple Bond Correlation (HMBC) Spectroscopic Studies
3.8. Fourier Transform Infrared (FT-IR) Spectroscopy
3.9. Differential Scanning Calorimetry (DSC) Analysis
3.10. Dissolution Studies
3.11. Cytotoxicity Studies
3.12. In Vivo Study
3.13. Ex vivo Study: Pharmacokinetic Analysis
3.14. Statistic
4. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Environment | DAS Solubility (mg/mL) | DAS Solubility (M) |
---|---|---|
HCl 0.05 M pH 1.2 | 4.31 × 10−2 | 8.84 × 10−5 |
Phosphate Buffer 0.05 M pH 7.4 | 7.65 × 10−4 | 1.56 × 10−6 |
Water | 6.49 × 10−4 | 1.33 × 10−6 |
Molar Ratio DAS: HP-β-CD | δ CH3 (Pyrimidine) | δ CH3 (Benzene) |
---|---|---|
1:0 | 2.498 | 2.292 |
1:1 | 2.513 | 2.293 |
1:10 | 2.534 | 2.294 |
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Cutrignelli, A.; Sanarica, F.; Lopalco, A.; Lopedota, A.; Laquintana, V.; Franco, M.; Boccanegra, B.; Mantuano, P.; De Luca, A.; Denora, N. Dasatinib/HP-β-CD Inclusion Complex Based Aqueous Formulation as a Promising Tool for the Treatment of Paediatric Neuromuscular Disorders. Int. J. Mol. Sci. 2019, 20, 591. https://doi.org/10.3390/ijms20030591
Cutrignelli A, Sanarica F, Lopalco A, Lopedota A, Laquintana V, Franco M, Boccanegra B, Mantuano P, De Luca A, Denora N. Dasatinib/HP-β-CD Inclusion Complex Based Aqueous Formulation as a Promising Tool for the Treatment of Paediatric Neuromuscular Disorders. International Journal of Molecular Sciences. 2019; 20(3):591. https://doi.org/10.3390/ijms20030591
Chicago/Turabian StyleCutrignelli, Annalisa, Francesca Sanarica, Antonio Lopalco, Angela Lopedota, Valentino Laquintana, Massimo Franco, Brigida Boccanegra, Paola Mantuano, Annamaria De Luca, and Nunzio Denora. 2019. "Dasatinib/HP-β-CD Inclusion Complex Based Aqueous Formulation as a Promising Tool for the Treatment of Paediatric Neuromuscular Disorders" International Journal of Molecular Sciences 20, no. 3: 591. https://doi.org/10.3390/ijms20030591