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 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.