The AAPS Journal

, Volume 19, Issue 1, pp 103–109 | Cite as

The Effect of Polymorphism on Surface Energetics of D-Mannitol Polymorphs

  • Robert R. Smith
  • Umang V. Shah
  • Jose V. Parambil
  • Daniel J. Burnett
  • Frank Thielmann
  • Jerry Y. Y. HengEmail author
Research Article Theme: Next Generation Formulation Design: Innovations in Material Selection and Functionality
Part of the following topical collections:
  1. Theme: Next Generation Formulation Design: Innovations in Material Selection and Functionality


The aim of this work was to assess the effect of different crystalline polymorphism on surface energetics of D-mannitol using finite dilution inverse gas chromatography (FD-IGC). Pure α, β and δ polymorphs were prepared via solution crystallisation and characterised by powder X-ray diffraction (P-XRD). The dispersive surface energies were found to range from 43 to 34 mJ/m2, 50 to 41 mJ/m2, and 48 to 38 mJ/m2 , for α, β, and δ, respectively, for surface coverage ranging from 0.006 to 0.095. A deconvolution modelling approach was employed to establish their energy sites. The primary sites corresponded to maxima in the dispersive surface energy of 37.1 and 33.5; 43.3 and 39.5; and 38.6, 38.4 and 33.0; for α, β, and δ, respectively. This methodology was also extended to an α-β polymorph mixture to estimate the amount of the constituent α and β components present in the sample. The dispersive surface energies of the α-β mixture were found to be in the range of 48 to 37 mJ/m2 with 40.0, 42.4, 38.4 and 33.1 mJ/m2 sites. The deconvolution modelling method extracted the energy contribution of each of the polymorphs from data for the polymorphic mixture. The mixture was found to have a β-polymorph surface content of ∼19%. This work shows the influence of polymorphism on surface energetics and demonstrates that FD-IGC coupled with a simple modelling approach to be a powerful tool for assessing the specific nature of this energetic distribution including the quantification of polymorphic content on the surface.


D-mannitol inverse gas chromatography modelling polymorphism powder X-ray diffraction surface energy heterogeneity 



The PhD studentship, supported by the Engineering and Physical Science Research Council and Surface Measurement Systems for Robert Smith, is gratefully acknowledged.


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Copyright information

© American Association of Pharmaceutical Scientists 2016

Authors and Affiliations

  • Robert R. Smith
    • 1
  • Umang V. Shah
    • 1
  • Jose V. Parambil
    • 1
  • Daniel J. Burnett
    • 2
  • Frank Thielmann
    • 3
  • Jerry Y. Y. Heng
    • 1
    Email author
  1. 1.Surfaces and Particle Engineering Laboratory, Department of Chemical EngineeringImperial College LondonLondonUK
  2. 2.Surface Measurement Systems Ltd.AllentownUSA
  3. 3.Novartis Pharma, Technical OperationsSteinSwitzerland

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