Quantitative analysis of amorphous content of lactose using CCD-Raman spectroscopy

A Raman spectroscopy method was developed for the quantification of the amorphous content of lactose. Both physical mixtures and spray-dried samples were used and the results were compared with the IMC determinations. Sample inhomogeneities were averaged out by collecting multiple spectra from each sample, and the total measurement time remained below 10 min due to the high sensitivity of the CCD-Raman spectrometer used in the measurements. The obtained calibration error (SEC) for the physical mixtures was 1.3% (w/w) in the 0-100% amorphous content range and was reduced to 0.2% (w/w) in the 0-10% range of more practical interest. The crystallization heat values of the spray-dried samples showed a linear correlation with the Raman quantifications in the amorphous content range of 0-80%, but saturated over the 80% concentration. This finding suggests a reference value of ca. 60 J/g for the spray-dried samples, instead of the crystallization heat of amorphous lactose (ca. 50 J/g) valid in the IMC determinations of physical mixtures.