Detection of low levels of amorphous lactose using H/D exchange and FT-Raman spectroscopy

Paul T. Whiteside, Shen Y. Luk, Claire E. Madden-Smith, Paul Turner, Nikin Patel, Michael W. George

Research output: Journal PublicationArticlepeer-review

14 Citations (Scopus)

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 (R2=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.

Original languageEnglish
Pages (from-to)2650-2656
Number of pages7
JournalPharmaceutical Research
Volume25
Issue number11
DOIs
Publication statusPublished - Nov 2008
Externally publishedYes

Keywords

  • Amorphous
  • Deuteration
  • Lactose
  • Quantification
  • Raman

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry
  • Pharmacology (medical)

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