Amorphous agomelatine stabilization in the presence of pyrogenic silica: Molecular mobility and intermolecular interaction studies
| Autor: | Panagiotis Barmpalexis, Elisavet Vardaka, Ioannis-Minas Moutafidis, Kyriakos Kachrimanis |
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| Rok vydání: | 2019 |
| Předmět: |
Materials science
Drug Compounding Pharmaceutical Science 02 engineering and technology Molecular Dynamics Simulation Kinetic energy 030226 pharmacology & pharmacy Excipients 03 medical and health sciences 0302 clinical medicine Differential scanning calorimetry Drug Stability Intermolecular interaction Acetamides Fourier transform infrared spectroscopy Fumed silica Calorimetry Differential Scanning Intermolecular force Temperature General Medicine Silicon Dioxide 021001 nanoscience & nanotechnology Amorphous solid Attenuated total reflection Physical chemistry Crystallization 0210 nano-technology Biotechnology |
| Zdroj: | European Journal of Pharmaceutics and Biopharmaceutics. 139:291-300 |
| ISSN: | 0939-6411 |
| DOI: | 10.1016/j.ejpb.2019.04.015 |
| Popis: | In the present work molecular mobility and intermolecular interactions were evaluated as two distinct mechanisms for amorphous agomelatine (AGM) stabilization in the presence of pyrogenic silica. Specifically, amorphous AGM properties related to molecular mobility in terms of relaxation time were calculated based on the Kohlrausch–Williams–Watts (KWW) and Adam-Gibbs (AG) equations, while the kinetic fragility index was calculated based on temperature-modulated differential scanning calorimetry (TM-DSC). Results showed that independently of the approach followed (KWW or AG) AGM’s molecular mobility was reduced in the presence of silica (KWW calculated stretched relaxation time constant, τβ, was 83.61 and 44.78 for AGM and AGM/silica dispersions; respectively, while AG-based initial relaxation time, τ0, at storage temperatures 40–50 K below AGM’s Tg was increased from six to eight days in the presence of silica); while kinetic fragility index values for amorphous AGM were reduced from 116.05 to 110.24 in the presence of silica. Additionally, MD simulations verified experimentally via attenuated total reflectance (ATR) FTIR spectroscopy, revealed the presence of significant intermolecular interactions between AGM and silica which act as an additional mechanism for amorphous AGM stabilization. |
| Databáze: | OpenAIRE |
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