Spatial characterization of hot melt extruded dispersion systems using thermal atomic force microscopy methods: The effects of processing parameters on phase separation

Jonathan G. Moffat, Sheng Qi, Duncan Q. M. Craig

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17 Citations (Scopus)


Purpose: In this study we explore the use of nano-scale localized thermal analysis (LTA) and transition temperature microcopy (TTM) as a novel combined approach to studying phase separation in HME dispersions of cyclosporine A in Eudragit EPO.

Methods: Modulated temperature differential scanning calorimetry (MTDSC), attenuated total reflectance FTIR spectroscopy, nano-LTA and TTM were performed on raw materials and dispersions prepared by hot melt extrusion (HME) and spin coating. For samples prepared by HME, two mixing temperatures (110°C and 150°C) and residence times (5 and 15 min) were investigated.

Results: Spin coated samples showed an intermediate T g for the mixed systems consistent with molecular dispersion formation. The HME samples prepared at 110°C showed evidence of inhomogeneity using MTDSC and FTIR, while those produced at 150°C h showed evidence for the formation of a single phase system using MTDSC. The nanothermal methods, however, indicated the presence of phase separated cyclosporine A at the higher preparation temperature while the TTM was able to map regions of differing penetration temperatures, indicating the presence of compositionally inhomogeneous regions in all but the high processing temperature/high residence time samples.

Conclusions: TTM is a potentially important new method for studying phase separation and that such separation may remain undetected or poorly understood using conventional bulk analytical techniques.
Original languageEnglish
Pages (from-to)1744-1752
Number of pages9
JournalPharmaceutical Research
Issue number7
Publication statusPublished - Jul 2014

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