Fig. 13.

Cocrystal solubility values approach drug solubility values with increasing solubilizing agent concentration, as shown for the CBZ-SAC cocrystal and carbamazepine dihydrate (CBZD) in SLS solutions. Cocrystal solubility advantage over drug decreases with increasing drug solubilization, and can reach a value above which cocrystal is less soluble than drug. The intersection of solubility curves represents a transition point. This transition point is characterized by a solubility value (S*) where S_cocrystal=S_drug and a solubilizing agent concentration referred to as critical stabilization concentration (CSC). Cocrystal or drug solubilities above S* indicate that the cocrystal is above the transition point and drug is more soluble than cocrystal. Curves represent simulations according to the solubility equations for cocrystal ${\mathrm{S}}_{\text{RHA},\mathrm{T}}=\sqrt{{\mathrm{K}}_{\text{sp}}(1+{\mathrm{K}}_{\mathrm{s}}^{\mathrm{R}}[\mathrm{M}])(1+\frac{{\mathrm{K}}_{\mathrm{a}}}{[{\mathrm{H}}^{+}]}+{\mathrm{K}}_{\mathrm{s}}^{\text{HA}}[\mathrm{M}]}$ and drug ${\mathrm{S}}_{\mathrm{R},\mathrm{T}}={\mathrm{S}}_{\mathrm{R},\text{aq}}(1+{\mathrm{K}}_{\mathrm{s}}^{\mathrm{R}}[\mathrm{M}])$ [69]. Adapted with permission from M. P. Lipert and N. Rodríguez-Hornedo from ref. [70]. Copyright 2015 American Chemical Society.