Pharmaceutical cocrystals use supramolecular synthons to construct non-covalent lattices with GRAS coformers to solve the solubility and bioavailability issues of BCS Class II/IV APIs, including hydrophobic herbal actives. In addition to evaluation by DSC, PXRD, FTIR, Higuchi-Connors solubility (2-14 fold enhancements, e.g., quercetin-caffeine electrospray 14x), dissolution kinetics, and ICH stability studies, this review covers solution-based (solvent evaporation, anti-solvent, cooling, slurry) and solid-state (neat/LAG grinding, melt) synthesis techniques. Despite difficulties such as excipient instability and phase transitions, benefits include green chemistry, IP extension, and better tabletability than salts for neutral APIs; Herbal cocrystals and synthetic APIs are listed in Tables 1-2, which provide cocrystals as a feasible option for rapid/sustained release formulations in contemporary drug delivery.
Kamble* et al. (2026) studied this question.