Twelve poorly water-soluble drugs in 384-well plates: a new EJPS study shows what second harmonic and linear light scattering reveal together about precipitation and drug-rich assemblies.
A new peer-reviewed study from ORYL Photonics and FHNW records second harmonic scattering (SHS) and linear light scattering (LLS) on the same supersaturated sample — the combined readout ORYL refers to as ultrafast light scattering (ULS).
Twelve poorly water-soluble drugs were prepared by DMSO solvent shift in 384-well plates and measured on a miniaturised platform driven by an ultrafast laser, then compared with apparent solubilities from parallel HPLC assays.
What the two signals showed
- LLS placed precipitation onsets close to or below the HPLC values, resolving particle formation down to approximately 0.1 µM for pimozide.
- SHS departed from LLS for lopinavir, loratadine and ritonavir, indicating largely centrosymmetric drug-rich assemblies above the solubility limit — droplet-like or amorphous domains confirmed by electron and confocal microscopy.
Precipitation assays tell you when a compound has crashed (precipitated) out of solution. A combined SHS and LLS readout in the same sample tells us what type of aggregate forms before precipitation – and where the two disagree, there is structure worth looking at: liquid-liquid phase separations, droplet-like or amorphous domains.
Orly Tarun, CEO & Co-founder, ORYL Photonics
Read the full paper here — European Journal of Pharmaceutical Sciences 225 (2026) 107624.