The effect of processing on the surface physical stability of amorphous solid dispersions

Sheng Qi, Jonathan Moffat, Duncan Craig, Ziyi Yang, Kathrin Nollenberger, Jessica Albers

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18 Citations (Scopus)

Abstract

The focus of this study was to investigate the effect of processing on the surface crystallization of amorphous molecular dispersions and gain insight into the mechanisms underpinning this effect. The model systems, amorphous molecular dispersions of felodipine-EUDRAGIT® E PO, were processed both using spin coating (an ultra-fast solvent evaporation based method) and hot melt extrusion (HME) (a melting based method). Amorphous solid dispersions with drug loadings of 10–90% (w/w) were obtained by both processing methods. Samples were stored under 75% RH/room temperatures for up to 10 months. Surface crystallization was observed shortly after preparation for the HME samples with high drug loadings (50–90%). Surface crystallization was characterized by powder X-ray diffraction (PXRD), ATR-FTIR spectroscopy and imaging techniques (SEM, AFM and localized thermal analysis). Spin coated molecular dispersions showed significantly higher surface physical stability than hot melt extruded samples. For both systems, the progress of the surface crystal growth followed zero order kinetics on aging. Drug enrichment at the surfaces of HME samples on aging was observed, which may contribute to surface crystallization of amorphous molecular dispersions. In conclusion it was found the amorphous molecular dispersions prepared by spin coating had a significantly higher surface physical stability than the corresponding HME samples, which may be attributed to the increased process-related apparent drug–polymer solubility and reduced molecular mobility due to the quenching effect caused by the rapid solvent evaporation in spin coating.
Original languageEnglish
Pages (from-to)897–908
Number of pages12
JournalEuropean Journal of Pharmaceutics and Biopharmaceutics
Volume88
Issue number3
Early online date8 Aug 2014
DOIs
Publication statusPublished - Nov 2014

Keywords

  • Amorphous molecular dispersions
  • Physical stability
  • Surface crystallization
  • Hot melt extrusion
  • Spin coating

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