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Updated: Aug 5, 2026
Synthesis and Characterization of Supramolecular Colloids
Published on: April 22, 2016
COMBINED SECOND HARMONIC AND LINEAR LIGHT SCATTERING AS A TOOL FOR SOLUBILITY AND AGGREGATION SCREENING
Jitka Kalasová1, Orly Tarun2, Martin Kuentz3
1University of Basel, Department of Pharmaceutical Sciences, Klingelbergstrasse 50 4052, Basel, Switzerland; University of Applied Sciences and Arts Northwest. Switzerland, School of Life Sciences, Institute for Pharma Technology and Biotechnology, Hofackerstr. 30 4132 Muttenz, Switzerland.
This study introduces a combined second harmonic scattering (SHS) and linear light scattering (LLS) optical platform for analyzing drug precipitation. The method offers sensitive detection and reveals complex aggregation pathways in supersaturated drug solutions.
Area of Science:
- Analytical Chemistry
- Materials Science
- Pharmaceutical Science
Background:
- Poor aqueous solubility of small-molecule drugs complicates analysis.
- Non-equilibrium conditions require rapid, material-sparing analytical tools.
- Understanding supersaturation and aggregation is crucial for drug development.
Purpose of the Study:
- To evaluate a miniaturized optical platform combining SHS and LLS for monitoring drug precipitation.
- To assess the platform's ability to capture incipient aggregation and phase separation.
- To investigate nonclassical aggregation pathways in supersaturated drug solutions.
Main Methods:
- Utilized an ultrafast 1030 nm laser-driven optical platform combining SHS and LLS.
- Monitored supersaturated solutions of 12 poorly water-soluble drugs prepared by DMSO solvent shift in 384-well plates.
- Compared LLS and SHS signals with HPLC apparent solubilities and orthogonal characterization methods.
Main Results:
- LLS detected precipitation onsets near or below HPLC values, with high sensitivity (down to ~0.1 µM for pimozide).
- SHS revealed complex peak-drop-rise patterns deviating from LLS, indicating distinct drug-rich assemblies.
- Orthogonal methods confirmed droplet-like or amorphous drug-rich domains preceding bulk precipitation.
Conclusions:
- The combined SHS-LLS platform enables highly sensitive precipitation detection.
- The platform reveals multistep, nonclassical aggregation pathways in pharmaceutical supersaturated systems.
- This approach provides rapid, material-sparing analysis for poorly soluble drugs.
