Characterization and quantification of amorphous material in milled and spray-dried salbutamol sulfate: A comparison of thermal, spectroscopic, and water vapor sorption approaches

Louise Grisedale, Matthew J. Jamieson, Peter S. Belton, Susan A. Barker, Duncan Q. M. Craig

Research output: Contribution to journalArticlepeer-review

34 Citations (Scopus)


A study has been undertaken using a range of established and novel approaches to examine the effects of milling on the structure and crystallization behavior of salbutamol sulfate. A combination of modulated temperature differential scanning calorimetry, attenuated total reflectance Fourier-transform infrared spectroscopy, powder X-ray diffraction, and gravimetric vapor sorption analysis have been employed, with a particular view to examining the validity of using spray-dried material as a comparator. Although the expected increase in amorphization with milling time was observed, several unexpected observations were made including an apparently anomalous relationship between glass transition temperature and water content; this was used as the basis for the development of a novel method of quantifying amorphous content. Reasonable agreement was found between the data obtained from the spectroscopic and thermal methods, particularly those latter approaches that do not rely on recrystallization for quantification. The activation energy for the onset process was determined and found to be similar for all materials studied. The study has indicated that when using spray-dried material as a standard, the associated limitations must be appreciated, particularly in terms of the assumption of comparability of the recrystallization process between materials that is embedded in many quantification techniques
Original languageEnglish
Pages (from-to)3114-3129
Number of pages16
JournalJournal of Pharmaceutical Sciences
Issue number8
Publication statusPublished - Aug 2011

Cite this