title: Quantification of residual crystallinity in ball milled commercially sourced lactose monohydrate by thermo-analytical techniques and terahertz spectroscopy.
abstract: 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 90min, 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 60min milling) and a slight increase at the 90min 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.
authors.affiliation: Leicester School of Pharmacy, De Montfort University, Leicester, United Kingdom. Electronic address: gsmith02@dmu.ac.uk.
authors.forename: Geoff
authors.initials: G
authors.lastname: Smith
authors.affiliation: Leicester School of Pharmacy, De Montfort University, Leicester, United Kingdom.
authors.forename: Amjad
authors.initials: A
authors.lastname: Hussain
authors.affiliation: University College of Pharmacy, University of the Punjab, Lahore, Pakistan.
authors.forename: Nadeem Irfan
authors.initials: NI
authors.lastname: Bukhari
authors.affiliation: Leicester School of Pharmacy, De Montfort University, Leicester, United Kingdom.
authors.forename: Irina
authors.initials: I
authors.lastname: Ermolina
mesh_terms: D002152:Calorimetry, Differential Scanning / Q000379:methods*; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003460:Crystallization; D007785:Lactose / Q000737:chemistry*; D055068:Terahertz Spectroscopy / Q000379:methods*; D013818:Thermogravimetry / Q000379:methods*; D013997:Time Factors
chemical_list: D007785:Lactose
keywords: Amorphous; Ball milling; Quantification; Relative residual crystallinity; Terahertz time domain spectroscopy; Thermal techniques