Co-Amorphous Simvastatin-Nifedipine with Enhanced Solubility for Possible Use in Combination Therapy of Hypertension and Hypercholesterolemia
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials
2.2. Sample Preparation
2.3. Thermal Characterization
2.4. Study of Storage Stability by XRD
2.5. Dissolution Profiles
2.6. Dissolution Kinetics Analysis by High Performance Liquid Chromatography (HPLC)
2.7. Structural Analysis by FTIR
3. Results and Discussion
3.1. Thermal Characterization
3.2. Results of Stability of the Amorphous State by PXRD
3.3. Results of Dissolution Profiles
3.4. Results of Structural Analysis by FTIR
4. Conclusions
Author Contributions
Acknowledgments
Conflicts of Interest
Abbreviations
ACS | American Chemical Society |
AR (ACS) | American Chemical Society Commitee on Analytical Reagents |
HT | Hypertension |
HCL | Hypercholesterolemia |
SIM | Simvastatin |
NIF | Nifedipine |
API | Active Pharmaceutical Principle |
DSC | Differential Scanning Calorimetry |
HPLC | High performance liquid chromatography |
FTIR | Fourier transform infrared spectroscopy |
PXRD | powder X-ray diffraction |
Tg | Glass Transition Tempeature |
Tm | Melting Temperature |
USP | United States Pharmacopeia. |
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Sample Availability: Amorphous samples prepared were consumed during characterization. All compounds were purchased from commercial sources and are not currently available from the authors. |
API | Illnes | Solubility | Permeability | BCS | Reference |
---|---|---|---|---|---|
Pravastatin | HCL | High | High | I | [5] |
Glimepiride | HCL | Low | High | II | [6] |
Atorvastatin | HCL | Low | High | II | [7] |
Simvastatin | HCL | Low | High | II | [5] |
Fenofibrate | HCL | Low | High | II | [8] |
Rosuvastatin | HCL | Low | High | II | [9] |
Gemfibrozil | HCL | Low | High | II | [10] |
Ezetimibe | HCL | Low | High | II | [11] |
Metoprolol | HT | High | High | I | [6] |
Telmisartan | HT | Low | High | II | [6] |
Losartan | HT | High | Low | III | [12] |
Irbesartan | HT | Low | High | II | [5] |
Sample | T/C | Tm/C | Tg/C |
---|---|---|---|
SIM | 136 | 30 | |
X | 122 | 132 | 26 |
X | 123 | 126 | 30 |
X | 124 | 133 | 35 |
X | 124 | 146 | 37 |
X | 124 | 157 | 42 |
X | 123 | 165 | 40 |
X | 124 | 170 | 42 |
NIF | 174 | 46 |
Drug | Sample | Deionized Water | Phosphate Buffer pH = 6.8 |
---|---|---|---|
Concentration of Dissolved Drug at 24 h (g/mL) | Concentration of Dissolved Drug at 24 h (g/mL) | ||
SIM | SIMc | ||
SIM–NIFa | |||
NIF | NIFc | ||
SIM–NIFa |
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Martínez-Jiménez, C.; Cruz-Angeles, J.; Videa, M.; Martínez, L.M. Co-Amorphous Simvastatin-Nifedipine with Enhanced Solubility for Possible Use in Combination Therapy of Hypertension and Hypercholesterolemia. Molecules 2018, 23, 2161. https://doi.org/10.3390/molecules23092161
Martínez-Jiménez C, Cruz-Angeles J, Videa M, Martínez LM. Co-Amorphous Simvastatin-Nifedipine with Enhanced Solubility for Possible Use in Combination Therapy of Hypertension and Hypercholesterolemia. Molecules. 2018; 23(9):2161. https://doi.org/10.3390/molecules23092161
Chicago/Turabian StyleMartínez-Jiménez, Cecilia, Jorge Cruz-Angeles, Marcelo Videa, and Luz María Martínez. 2018. "Co-Amorphous Simvastatin-Nifedipine with Enhanced Solubility for Possible Use in Combination Therapy of Hypertension and Hypercholesterolemia" Molecules 23, no. 9: 2161. https://doi.org/10.3390/molecules23092161