Detection of Low Levels of Amorphous Lactose using H/D Exchange and FT-Raman Spectroscopy

Purpose To demonstrate the potential of monitoring H/D exchange by FT-Raman spectroscopy as a tool for the detection and quantification of low levels of amorphous lactose in formulations. Methods Samples containing different proportions of amorphous and crystalline lactose were prepared. H/D exchang...

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Bibliographic Details
Published in:Pharmaceutical research 2008-11, Vol.25 (11), p.2650-2656
Main Authors: Whiteside, Paul T., Luk, Shen Y., Madden-Smith, Claire E., Turner, Paul, Patel, Nikin, George, Michael W.
Format: Article
Language:English
Subjects:
Biochemistry
Biological and medical sciences
Biomedical and Life Sciences
Biomedical Engineering and Bioengineering
Biomedicine
Deuterium
General pharmacology
Hydrogen
Lactose
Lactose - analysis
Medical Law
Medical sciences
Pharmaceutical technology. Pharmaceutical industry
Pharmacology
Pharmacology. Drug treatments
Pharmacology/Toxicology
Pharmacy
Research Paper
Spectrum analysis
Spectrum Analysis, Raman - methods
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Summary:Purpose To demonstrate the potential of monitoring H/D exchange by FT-Raman spectroscopy as a tool for the detection and quantification of low levels of amorphous lactose in formulations. Methods Samples containing different proportions of amorphous and crystalline lactose were prepared. H/D exchange was carried out by exposing the samples to a flow of D 2 O vapour. A calibration curve was constructed from the FT-Raman spectra of the deuterated samples by integrating the ν(OD) band and normalizing to an internal standard. This method was benchmarked against a conventional approach using Raman spectroscopy where the ratio of Raman bands associated with crystalline and amorphous lactose is used to estimate the amorphous content. Results The H/D exchange method revealed a linear response over the entire composite range with an excellent correlation coefficient ( R 2  = 0.999). The sensitivity of this approach in detecting the amount of amorphous lactose present in a blend is significantly greater than that offered by conventional FT-Raman in the 0–10% level of amorphous material. Conclusions A non-destructive method that is capable of providing reproducible measurements of low levels of amorphous material in lactose has been demonstrated and this method has enhanced sensitivity relative to approaches using Raman spectroscopy without deuteration.
ISSN:0724-8741
1573-904X
DOI:10.1007/s11095-008-9682-4