Solvent Redistribution Method To Determine Solubility and Aggregation: High Throughput, Accuracy, and Sustainability.

Area of Science:

• Pharmaceutical Science
• Green Chemistry
• Materials Science

Background:

• The pharmaceutical industry contributes significantly to global CO2 emissions, with drug discovery assays being major waste generators.
• Current solubility measurement methods are either energy-intensive and slow (e.g., HPLC) or fast but inaccurate (e.g., turbidity).
• There is a critical need for sustainable, accurate, and high-throughput methods in drug discovery.

Purpose of the Study:

• To develop a novel, highly sensitive, and sustainable assay for measuring drug solubility and aggregation.
• To reduce the environmental impact and CO2 footprint of pharmaceutical research and development.
• To achieve a significant improvement in the detection limit for solubility measurements.

Main Methods:

• Utilized high-throughput angle-resolved second harmonic scattering to detect nanoscale interfacial fluctuations.
• Applied classical nucleation theory and nonlinear light scattering modeling to analyze solvent interfacial area changes.
• Exploited the coherent nature of second harmonic emission for sensitive detection.

Main Results:

• Demonstrated a thousandfold increase in sensitivity for solubility/aggregation detection, lowering the limit from ~1 μM to ~1 nM.
• Established a correlation between solvent interfacial area fluctuations and aggregation onset.
• Achieved a substantial sustainability gain in solubility assay methodology.

Conclusions:

• The novel scattering-based method offers a highly sensitive, accurate, and sustainable alternative for solubility measurements.
• This technique has the potential to significantly reduce the pharmaceutical industry's CO2 emissions by approximately 3.5%.
• The findings pave the way for greener drug discovery and development processes.