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Updated: Apr 25, 2026

Molten-Salt Synthesis of Complex Metal Oxide Nanoparticles
Published on: October 27, 2018
Salt stability--effect of particle size, relative humidity, temperature and composition on salt to free base
Yi-Ling Hsieh1, Lynne S Taylor
1Department of Industrial and Physical Pharmacy, Purdue University, 575 Stadium Mall Dr., 47907, West Lafayette, Indiana, USA.
Purpose:
The aim of this study was to investigate how factors such as temperature, relative humidity and particle size impact the extent of disproportionation (salt to free base conversion) in powder blends of miconazole, benzocaine or sertraline mesylate salts mixed with a basic additive.
Method:
Raman spectroscopy was used to quantitate the extent of disproportionation. The data was further analyzed by multivariate analysis with partial least squares (PLS) modeling.
Results:
It was found that salt disproportionation was significantly influenced by % weight gain due to moisture sorption both in terms of the kinetics and the conversion extent, suggesting a solution-mediated reaction. Temperature plays an important role in impacting the value of pHmax which in turn has a significant correlation to the amount of free base formed. The particle size and drug: additive ratio were also found to influence the extent of disproportionation.
Conclusions:
This study shows that the extent of salt disproportionation is influenced by multiple factors and the application of PLS modeling demonstrated the feasibility of utilizing multivariate analysis to generate a predictive model for estimating the extent of conversion and thus may serve as a tool for risk assessment.
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