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Accelerated Forced Degradation of Pharmaceuticals in Levitated Microdroplet Reactors
Author(s) -
Li Yangjie,
Liu Yong,
Gao Hong,
Helmy Roy,
Wuelfing W. Peter,
Welch Christopher J.,
Cooks R. Graham
Publication year - 2018
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201801176
Subject(s) - degradation (telecommunications) , chemistry , levitation , yield (engineering) , acceleration , solvent , boiling , leidenfrost effect , chemical engineering , chromatography , thermodynamics , organic chemistry , mechanical engineering , computer science , engineering , telecommunications , physics , classical mechanics , magnet , heat transfer , heat transfer coefficient , nucleate boiling
Forced degradation is a method of studying the stability of pharmaceuticals in order to design stable formulations and predict drug product shelf life. Traditional methods of reaction and analysis usually take multiple days, and include LC‐UV and LC‐MS product analysis. In this study, the reaction/analysis sequence was accelerated to be completed within minutes using Leidenfrost droplets as reactors (acceleration factor: 23–188) and nanoelectrospray ionization MS analysis. The Leidenfrost droplets underwent the same reactions as seen in traditional bulk solution experiments for three chemical degradations studied. This combined method of accelerated reaction and analysis has the potential to be extended to forced degradation of other pharmaceuticals and to drug formulations. Control of reaction rate and yield is achieved by manipulating droplet size, levitation time and whether or not make‐up solvent is added. Evidence is provided that interfacial effects contribute to rate acceleration.