Abstract/Summary

The aim of this contribution is to examine the impact of incorporating surfactants into amorphous solid dispersions on solid state miscibility and aqueous solubility of the antifungal drug griseofulvin. Spray dried amorphous solid dispersions of griseofulvin (GF) and hypromellose acetate succinate (HPMCAS) were prepared by spray drying. Three different surfactants of varying ratios between 1 to 5% were used namely the anionic sodium dodecyl sulfate (SDS), the cationic dodecyletrimethylammonium bromide (DTAB) and the non-ionic pluronic (F127). Flory-Huggins model combined with calculations based on Hoffman's equation were used to calculate miscibility and predicted solubility of the amorphous form. The results showed that the prepared solid dispersions exhibited enhanced drug-polymer miscibility reflected by improved thermodynamics of mixing. The highest miscibility was achieved when DTAB was incorporated by which the drug-polymer miscibility was enhanced by approximately 1.5 times. The tendency to recrystallize was calculated using reduced recrystallization parameter and correlated with the measured saturation solubility showing distinct properties which were dependent on the type of surfactant. Saturated solubility of the solid dispersions was compared with micellar solubility and was found to be significantly affected by the presence of the polymer. The glass transition temperature (Tg) decreased significantly upon the addition of surfactants. However, gravimetric analysis showed that solvent content did not exceed 1% which suggests that the shifted Tg was not related to plasticizing effect of residual solvent. Overall, these results suggest potential role for the surfactants in enhancing solid state miscibility when incorporated into the solid dispersions.