The use of election paramagnetic resonance spectroscopy in early preformulation experiments: the impact of different experimental formulations on the release of a lipophilic spin probe into gastric juice.
The lipophilic spin probe TEMPOL-benzoate was dissolved in different experimental formulations, including polyethylene glycol 400 (PEG 400), Miglyol, glycerol monooleate (GMO), and Cremophor RH-40. Samples were measured by electron paramagnetic resonance (EPR) spectroscopy before and after addition to human gastric juice. The distance between the first and the third peak in the EPR spectrum (2a(N)) was measured to monitor the polarity of the spin probe's microenvironment. Moreover, the ratio between the signal amplitudes of the second and the third peak (a/b ratio) was used to monitor the mobility of the spin probe in a certain formulation. Thus, by calculating 2a(N) and the a/b ratio of the EPR spectra it was possible to determine a potential release of the spin probe from different formulations into gastric juice. It was found that oily and surface-active vehicles (Miglyol, Cremophor RH-40, and GMO) were more suitable to protect a lipophilic compound from being released within a gastric environment than PEG 400. Our results demonstrate that EPR spectroscopy seems to be a promising tool in early preformulation experiments to monitor the release of spin probes from formulations of different nature. This kind of experiment can be of value for the optimization of exploratory formulations.
Pharmaceuticals Division, F. Hoffmann-La Roche Ltd., CH-4070 Basel, Switzerland, beate.bittner@roche.com
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D002626:Chemistry, Pharmaceutical; D003497:Cyclic N-Oxides; D004578:Electron Spin Resonance Spectroscopy; D005750:Gastric Juice / Q000378:metabolism*; D005989:Glycerides; D006801:Humans; D015394:Molecular Structure; D014677:Pharmaceutical Vehicles; D011092:Polyethylene Glycols; D012997:Solvents; D013113:Spin Labels
D003497:Cyclic N-Oxides; D005989:Glycerides; D014677:Pharmaceutical Vehicles; D012997:Solvents; D013113:Spin Labels; C022131:cremophor; D011092:Polyethylene Glycols; C005953:monoolein; C001803:tempol