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

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Abstract

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 D2O 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.

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Acknowledgements

The authors wish to thank the KTP for financial support of this project. Mr. Martin Dellar of the School of Chemistry, The University of Nottingham and Mr. John Fisher of Triton Technology are thanked for their assistance in the design and development of the dynamic deuteration apparatus. We are grateful to Mr. Andrew Camenisch and Ms. Abigail Shapland for their preliminary experimental work.

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Authors and Affiliations

  1. Molecular Profiles Ltd, 8 Orchard Place, Nottingham Business Park, Nottingham, NG8 6PX, United Kingdom

    Paul T. Whiteside, Shen Y. Luk, Claire E. Madden-Smith & Nikin Patel

  2. School of Chemistry, The University of Nottingham, University Park, Nottingham, NG7 2RD, United Kingdom

    Michael W. George

  3. Bruker Optics Ltd, Banner Lane, Coventry, CV4 9GH, United Kingdom

    Paul Turner

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  1. Paul T. Whiteside
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Correspondence to Paul T. Whiteside or Michael W. George.

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Whiteside, P.T., Luk, S.Y., Madden-Smith, C.E. et al. Detection of Low Levels of Amorphous Lactose using H/D Exchange and FT-Raman Spectroscopy. Pharm Res 25, 2650–2656 (2008). https://doi.org/10.1007/s11095-008-9682-4

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  • DOI: https://doi.org/10.1007/s11095-008-9682-4

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