Quantification of residual crystallinity in ball milled commercially sourced lactose monohydrate by thermo-analytical techniques and terahertz spectroscopy

• DSC curves of milled lactose monohydrate in contrast to that of un-milled one, show the melting peak of β-lactose.
• TGA and two DSC methods overestimate the residual crystallinity of milled lactose monohydrate.
• THz spectra of un-milled lactose monohydrate show the peaks of both alpha and beta forms.
• Long milled samples show the THz peaks of alpha lactose only.
• The estimates of residual crystallinity by DSC method 1 and THz broadly agree.

The quantification of crystallinity is necessary in order to be able to control the milling process. The use of thermal analysis for this assessment presents certain challenges, particularly in the case of crystal hydrates. In this study, the residual crystallinity on ball milling of lactose monohydrate (LMH), for periods up to 90 min, was evaluated by thermo-analytical techniques (TGA, DSC) and terahertz spectroscopy (THz). In general, the results from one of the DSC analysis and the THz measurements agree showing a monotonous decrease in relative residual crystallinity with milling time (∼80% reduction after 60 min milling) and a slight increase at the 90 min time point. However, the estimates from TGA and two other methods of analyzing DSC curve do not agree with the former techniques and show variability with significantly higher estimates for crystallinity. It was concluded that, the thermal techniques require more complex treatment of the data in the evaluation of changes in crystallinity of a milled material (in particular to account for the de-vitrification and mutarotation of the material that inevitably occurs during the measurement cycle) while the analysis of THz data is more straightforward, with the measurement having no impact on the native state of the material.

Comparison of estimates of residual crystallinity in ball milled lactose monohydrate as measured by DSC and THz Spectroscopy.Figure optionsDownload high-quality image (84 K)Download as PowerPoint slide