Table 3.
NVP cocrystals: Ksp, pHmax, and Scocrystal/Sdrug.
| Cocrystal | Kspa (M2 or M3) b | pHmaxc | Scocrystal/Sdrugd pH 1 to 5 |
Scocrystal/Sdruge pH ? |
|---|---|---|---|---|
| NVP-MLE (1:1) | (2.0±0.5) × 10−5 | none | 3.4–906 | 5.3 |
| NVP-SAC (2:1) | (1.0±0.6) × 10−10 | 1.1 | 0.9–47 | 1.4 |
| NVP-SLC (2:1) | (4.0±0.9) × 10−11 | 1.7 | 0.6–11 | 1.1 |
a
Calculated from equilibrium solubility measurements at cocrystal/drug eutectic points at 25°C.
b
Units of M2 for 1:1 and M3 for 2:1 cocrystals.
c
Obtained from the intercept of drug and cocrystal solubility curves in Fig. 14.
d
Obtained from equilibrium solubility calculation, S vs pH curves in Fig. 14.
e
From Caira et al., [31] obtained from cocrystal dissolution in water, pH unknown, and NVP solubility in water (0.36mM) at 37°C. The influence of temperature on Scocrystal/Sdrug is expected to be small compared to the influence of pH. Sdrug hydrate increases by about 2 fold between 25 and 37°C [75] and the change in Scocrystal/Sdrug may be even smaller if at all.