Early stage phase separation in pharmaceutical solid dispersion thin films under high humidity: Improved spatial understanding using probe-based thermal and spectroscopic nanocharacterization methods

Sheng Qi, Jonathan G. Moffat, Ziyi Yang

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56 Citations (Scopus)


Phase separation in pharmaceutical solid dispersion thin films under high humidity is still poorly understood on the submicrometer scale. This study investigated the phase separation of a model solid dispersion thin film, felodipine-PVP K29/32, prepared by spin-coating and analyzed using probe-based methods including atomic force microscopy, nanothermal analysis, and photothermal infrared microspectroscopy. The combined use of these techniques revealed that the phase separation process occurring in the thin films under high humidity is different from that in dry conditions reported previously. The initial stage of phase separation is primarily initiated in the bulk of the films as amorphous drug domains. Drug migration toward the surface of the solid dispersion film was then observed to occur under exposure to increased humidity. PVP cannot prevent phase separation of felodipine under high humidity but can minimize the crystallization of amorphous felodipine domains in the solid dispersion thin films. This study demonstrates the unique abilities of these nanocharacterization methods for studying, in three dimensions, the phase separation of thin films for pharmaceutical applications.
Original languageEnglish
Pages (from-to)918-930
Number of pages13
JournalMolecular Pharmaceutics
Issue number3
Early online date28 Jan 2013
Publication statusPublished - 4 Mar 2013

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