A novel approach for measuring room temperature enthalpy of mixing and associated solubility estimation of a drug in a polymer matrix
| Autor: | Haichen Nie, Patrick J. Marsac, Yongchao Su, Hang Lau, Nico Setiawan, Lynne S. Taylor, Matthew K. Defrese, Jonas Alin, James DiNunzio, Hanmi Xi, Nathan Hesse, Lisa Lupton |
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| Rok vydání: | 2018 |
| Předmět: |
chemistry.chemical_classification
Materials science Polymers and Plastics Organic Chemistry Thermodynamics 02 engineering and technology Polymer Flory–Huggins solution theory 021001 nanoscience & nanotechnology Enthalpy of mixing 030226 pharmacology & pharmacy Amorphous solid law.invention 03 medical and health sciences 0302 clinical medicine chemistry law Materials Chemistry Organic chemistry Crystallization Solubility 0210 nano-technology Dissolution Mixing (physics) |
| Zdroj: | Polymer. 135:50-60 |
| ISSN: | 0032-3861 |
| DOI: | 10.1016/j.polymer.2017.11.056 |
| Popis: | The utility of amorphization of drug molecules, such as enhanced solubility, dissolution rate and oral bioavailability, has been well exemplified in the literature. Yet, the application of this technique is often hindered by the crystallization liability of the drug. Amorphous solid dispersions (ASD), in which polymers are mixed with the amorphous drug, are often utilized to maintain the amorphous form. Several approaches have been illustrated in the literature to quantify the degree of mixing of drug and polymer. Although successful quantification has been demonstrated, all of these approaches probe the mixing energies at temperatures close to the melting temperature and, thus, require an extrapolation to room/storage temperature. Hence, an approach to directly estimate the drug-polymer extent of mixing at room temperature would enable a more accurate prediction of the physical stabilities. Herein, solution calorimetry was used to determine enthalpies of mixing of drug and polymer dispersions. These are necessary for the estimation of the Flory-Huggins interaction parameter, and associated free energy of mixing function. The estimated free energy of mixing, in turn, enabled the calculation of the drug solubility in the polymer system, which is a critical thermodynamic parameter in predicting the physical stability of an ASD. |
| Databáze: | OpenAIRE |
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