The role of pH and dose/solubility ratio on cocrystal dissolution, drug supersaturation and precipitation
| Autor: | Gislaine Kuminek, Simone Gonçalves Cardoso, Naír Rodríguez-Hornedo, Tatiane Cogo Machado |
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| Rok vydání: | 2020 |
| Předmět: |
Supersaturation
Chemistry Precipitation (chemistry) Cmax Pharmaceutical Science Disproportionation 02 engineering and technology Hydrogen-Ion Concentration 021001 nanoscience & nanotechnology Meloxicam 030226 pharmacology & pharmacy Cocrystal 03 medical and health sciences Drug Liberation 0302 clinical medicine Solubility 0210 nano-technology Crystallization Dissolution Eutectic system Nuclear chemistry |
| Zdroj: | European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences. 152 |
| ISSN: | 1879-0720 |
| Popis: | Cocrystals that are more soluble than the constituent drug, generate supersaturation levels during dissolution and are predisposed to conversion to the less soluble drug. Drug release studies during cocrystal dissolution generally compare several cocrystals and their crystal structures. However, the influence of drug dose and solubility in different dissolution media has been scarcely reported. The present study aims to investigate how drug dose/solubility ratio (Do=Cdose/Sdrug), cocrystal solubility advantage over drug (SA=Scocrystal/Sdrug), and dissolution media affect cocrystal dissolution-drug supersaturation and precipitation (DSP) behavior. SA and Ksp values of 1:1 cocrystals of meloxicam-salicylic acid (MLX-SLC) and meloxicam-maleic acid (MLX-MLE) were determined at cocrystal/drug eutectic points. Results demonstrate that both cocrystals enhance SA by orders of magnitude (20 to 100 times for the SLC and over 300 times for the MLE cocrystal) in the pH range of 1.6 to 6.5. It is shown that during dissolution, cocrystals regulate the interfacial pH (pHint) to 1.6 for MLX-MLE and 4.5 for MLX-SLC, therefore diminishing the cocrystal dissolution rate dependence on bulk pH. Do values ranged from 2 (pH 6.5) to 410 (pH 1.6) and were mostly determined by the drug solubility dependence on pH. Drug release profiles show that maximum supersaturation (σmax=Cmax/Sdrug)and AUC increased with increasing Do as pH decreased. When Do>>SA, the cocrystal solubility is not sufficient to dissolve the dose so that a dissolution-precipitation quasi-equilibrium state is able to sustain supersaturation for the extent of the experiment (24 h). When Do |
| Databáze: | OpenAIRE |
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