18β-glycyrrhetinic acid as a promising co-former for co-amorphous systems fabrication.

Co-amorphous systems (CASs) effectively enhance the solubility of poorly soluble drugs, but their development is often limited by the scarcity and inadequate co-amorphization capability of existing co-formers, resulting in poor physical stability and limited clinical applicability. Therefore, identifying new co-formers is essential. In this study, 18β-glycyrrhetinic acid (GA), a natural licorice-derived sweetener, was evaluated as a co-former for CAS development using basic albendazole, neutral carbamazepine, and acidic indomethacin as model drugs. GA exhibited excellent amorphization capability, achieving complete amorphization within 30 min of cryogrinding. In the presence of GA, all three drugs were fully amorphized within a short cryogrinding time, whereas amorphization remained incomplete after 5 h without GA. Modulated differential scanning calorimetry confirmed homogeneous CAS formation, with elevated glass transition temperatures (93.46-114.43 °C), while Fourier transform infrared spectroscopy revealed strong intermolecular interactions. All CASs exhibited higher maximum drug concentrations than their crystalline counterparts in supersaturated dissolution tests. In addition, no recrystallization was observed after storage under 75 % relative humidity for 6 months or dry conditions for 12 months at 25 °C, demonstrating excellent physical stability. These findings identify GA as a promising co-former for expanding the design space of CASs.