Mechanistic Analysis of Cocrystal Dissolution as a Function of pH and Micellar Solubilization
| Autor: | Naír Rodríguez-Hornedo, Gregory E. Amidon, Fengjuan Cao, Gordon L. Amidon |
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| Rok vydání: | 2016 |
| Předmět: |
interfacial pH
Diffusion micellar solubilization Inorganic chemistry Pharmaceutical Science diffusions 02 engineering and technology 030226 pharmacology & pharmacy Chemical reaction Cocrystal Micelle Article law.invention 03 medical and health sciences Saccharin 0302 clinical medicine Drug Stability X-Ray Diffraction Pulmonary surfactant law Drug Discovery cocrystal dissolution modeling Crystallization Solubility Dissolution Micelles Calorimetry Differential Scanning Chemistry Hydrogen-Ion Concentration 021001 nanoscience & nanotechnology Carbamazepine Thermodynamics Molecular Medicine flux predictions Salicylic Acid 0210 nano-technology Powder Diffraction mass transport analysis |
| Zdroj: | Molecular Pharmaceutics |
| ISSN: | 1543-8392 1543-8384 |
| Popis: | The purpose of this work is to provide a mechanistic understanding of the dissolution behavior of cocrystals under the influence of ionization and micellar solubilization. Mass transport models were developed by applying Fick’s law of diffusion to dissolution with simultaneous chemical reactions in the hydrodynamic boundary layer adjacent to the dissolving cocrystal surface to predict the pH at the dissolving solid–liquid interface (i.e., interfacial pH) and the flux of cocrystals. To evaluate the predictive power of these models, dissolution studies of carbamazepine–saccharin (CBZ-SAC) and carbamazepine–salicylic acid (CBZ-SLC) cocrystals were performed at varied pH and surfactant concentrations above the critical stabilization concentration (CSC), where the cocrystals were thermodynamically stable. The findings in this work demonstrate that the pH dependent dissolution behavior of cocrystals with ionizable components is dependent on interfacial pH. This mass transport analysis demonstrates the importance of pH, cocrystal solubility, diffusivity, and micellar solubilization on the dissolution rates of cocrystals. |
| Databáze: | OpenAIRE |
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