Measurement of lactose crystallinity using Raman spectroscopy

Raman spectroscopy (RS) was used to determine the crystallinity of lactose (a commonly used carrier in dry powder inhaler (DPI) formulations). Samples of alpha-lactose monohydrate and amorphous lactose were prepared using ethanol precipitation and lyophilisation respectively. The anomeric forms were confirmed using DSC at a rate of 10 degrees C/min and heated to 250 degrees C. The Raman spectra of both alpha-lactose monohydrate and amorphous lactose were obtained. Distinguishable differences were seen between the two spectra including peak areas and intensities. Depolarisation ratios (rho) of each form were then determined to identify the crystallinity of the lactose carrier samples. At the prominent Raman bands 865 and 1082 cm-1, significant differences in rho values were observed for crystalline (0.80+/-0.07, 0.89+/-0.06 respectively) and amorphous samples (0.44+/-0.07, 0.51+/-0.10).