Application Brief: Water-Induced Phase Separation of Miconazole-Poly (Vinylpyrrolidone-Co-Vinyl Acetate) Amorphous Solid Dispersions: Insights with Confocal Fluorescence Microscopy

August 31, 2017

Key Points

  • Researchers from Purdue University used AFM-IR to analyze miconazole:PVPVA miscibility under different conditions at stages of its production
  • The blend showed a positive correlation between water exposure and immiscibility
  • This study offers a useful approach to evaluate drug-polymer homogeneity, and will help to determine useful production methods


S. Sugandha and L. S. Taylor


The aim of this study was to evaluate the utility of confocal fluorescence microscopy (CFM) to study the water-induced phase separation of miconazole-poly (vinylpyrrolidone-co-vinyl acetate) (mico-PVPVA) amorphous solid dispersions (ASDs), induced during preparation, upon storage at high relative humidity (RH) and during dissolution. Different fluorescent dyes were added to drug-polymer films and the location of the dyes was evaluated using CFM. Orthogonal techniques, in particular atomic force microscopy (AFM) coupled with nanoscale infrared spectroscopy (AFM-nanoIR), were used to provide additional analysis of the drug-polymer blends. The initial miscibility of mico-PVPVA ASDs prepared under low humidity conditions was confirmed by AFM-nanoIR. CFM enabled rapid identification of drug-rich and polymer-rich phases in phase separated films prepared under high humidity conditions. The identity of drug- and polymer-rich domains was confirmed using AFM-nanoIR imaging and localized IR spectroscopy, together with Lorentz contact resonance (LCR) measurements. The CFM technique was then utilized successfully to further investigate phase separation in mico-PVPVA films exposed to high RH storage and to visualize phase separation dynamics following film immersion in buffer. CFM is thus a promising new approach to study the phase behavior of ASDs, utilizing drug and polymer specific dyes to visualize the evolution of heterogeneity in films exposed to water.

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