Aqueous solubility is essential for drug absorption and bioavailability, but current assays face trade-offs between accuracy, sensitivity, speed, and resource use. In this study with our partners FHNW and CSEM, we present a novel solubility assessment method using our non-resonant second harmonic scattering (SHS), which detects water molecule fluctuations around solutes. The apparent solubility of 14 poorly soluble drugs measured by SHS strongly correlated with traditional HPLC data (r = 0.9273). The study also evaluated each compound’s supersaturation propensity and linked this behavior to their thermal properties, with ketoconazole and tamoxifen showing the highest supersaturation. The SHS method effectively identified micelle formation, both in a reference surfactant and in several drugs, indicating self-assembly above the solubility limit. Overall, SHS is shown to be a promising, high-throughput, and resource-efficient technique for solubility and aggregation studies at the molecular level.
Scientific Publication
