Applications brief: Water-induced phase separation of miconazole-poly(vinylpyrrolidone-co-vinyl acetate) amorphous solid dispersions: Insights with confocal fluorescence microscopy

Key results

  • 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

Key words

AFM-IR | Polymers | Pharmaceutical | Miconazole | Drug miscibility


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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AFM image of 50:50 Mico:PVPVA phase separated film prepared at 60% relative humidity, and IR spectra obtained from discrete (red) and continuous (green) phases of phase separated films of 50:50 Mico:PVPVA. The relative peak height of the characteristic drug peak at 1590 cm-1 is higher for the discrete phase as compared to the continuous phase, whereas the relative peak height of the polymer specific peak at 1679 cm-1 is higher in the continuous phase as compared to discrete phase. This indicates that the discrete phase is miconazole-rich, whereas the continuous phase is PVPVA-rich.

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