Related Experiment Video
Updated: Dec 18, 2025
09:59
Coherent anti-Stokes Raman Scattering CARS Microscopy Visualizes Pharmaceutical Tablets During Dissolution
Published on: July 4, 2014
18.5K
Machine-Vision-Enabled Salt Dissolution Analysis
Jernej Štukelj1,2, Mikael Agopov2, Jouko Yliruusi2
1Drug Research Program and Division of Pharmaceutical Chemistry and Technology, University of Helsinki, Viikinkaari 5E, 00790 Helsinki, Finland.
Analytical Chemistry
|June 17, 2020
Summary
Drug salt selection requires understanding dissolution behavior. A machine-vision single-particle analysis (SPA) method rapidly characterizes salt dissolution, including disproportionation, using minimal sample amounts for improved drug development.
Area of Science:
- Pharmaceutical Sciences
- Physical Chemistry
- Materials Science
Background:
- Salt formation enhances solubility of ionizable drugs.
- Drug salt disproportionation can drastically alter solubility and bioavailability.
- Understanding salt dissolution behavior is crucial for drug salt selection.
Purpose of the Study:
- To introduce a machine-vision-based single-particle analysis (SPA) method for characterizing drug salt dissolution.
- To demonstrate SPA's ability to analyze dissolution behavior with low sample consumption.
- To investigate the disproportionation process and its impact on drug solubility and solid-state form.
Main Methods:
- Utilized machine-vision-based single-particle analysis (SPA).
- Performed simultaneous screening of small sample amounts (<1 mg).
- Analyzed pH-solubility profiles, intrinsic solubility, common-ion effect, pKa, pHmax, and Ksp values.
Main Results:
- SPA successfully determined key dissolution parameters for three model compounds.
- Observed in situ disproportionation processes at particle-scale resolution.
- Identified a high-energy form of diclofenac free acid and liquid verapamil free base upon disproportionation.
Conclusions:
- SPA provides a low sample consumption platform for rapid and detailed characterization of drug salt dissolution behavior.
- SPA enables in situ observation of disproportionation and its effects on morphology and solubility.
- This method aids in understanding and optimizing drug salt selection processes.
