Table 2.
Solubility of ketoconazole (KTZ) base, ketoconazole-fumaric acid cocrystal and ketoconazole-succinic acid cocrystal in different buffer solutions along with initial pH of buffers and pH after equilibration with solids. Solubility represent average of three determinations (± standard deviation).
| Initial pH and buffers used | Ketoconazole (KTZ) | KTZ-fumaric acid cocrystal | KTZ-succinic acid cocrystal | |||
|---|---|---|---|---|---|---|
| pH after equilibration | Solubility (mg/mL) | pH after equilibration | Solubility (mg/mL) | pH after equilibration | Solubility (mg/mL) | |
| pH 1.1 (0.1 M HCl) | 2.9* | 27* | 2.03± 0.01 | 21.54± 0.55 | 2.52± 0.05 | 23.99± 0.30 |
| pH 2.1 HCl/KCl buffer | 3.6* | 3.4* | 2.89 ± 0.02 | 3.39± 0.02 | 3.38 ± 0.00 | 3.69± 0.07 |
| pH 5.0 acetate buffer | 4.95 | 0.13 | 4.31 ± 0.02 | 0.60± 0.02 | 4.60± 0.02 | 0.38± 0.03 |
| pH 7.9 phosphate buffer | 7.82±0.01 | 0.001±0.000 | 7.17 ± 0.01 | 0.003± 0.002 | 7.14 ± 0.01 | 0.006± 0.001 |
*Approximate pH and solubility. As more solid materials are added, pH shifts and solubility changes.