Spray-dried paracetamol/polyvinylpyrrolidone amorphous solid dispersions: Part II - Solubility and in vitro drug...

Amorphous solid dispersions (ASDs) comprising an active pharmaceutical ingredient (API) and polymer are a frequently described approach in the formulation of new drug candidates. This study aimed to evaluate the saturation solubility and dissolution behavior of ASDs consisting of paracetamol (PCM) and polyvinylpyrrolidone/vinyl acetate (PVP/VA) in water and their influence on the transepithelial in vitro permeation of PCM. With increasing amounts of PVP/VA, the water solubility of ASDs containing PCM increased up to six times compared to that of a saturated PCM solution. In the case of preparations with 30 % PCM, two-phase separation was observed in water at room temperature, consisting of a polymer-rich phase with high API loading and an aqueous, polymer-poor phase. This result was attributed to the thermoresponsive behavior of PVP/VA with lower critical solution temperature (LCST). As the PCM content in the ASD increased, the LCST decreased. This behavior was analyzed by measuring the demixing temperature (T_dem) values with differential scanning calorimetry (DSC). Furthermore, the permeation behavior of PCM from these phase-separated preparations through Caco-2 cells was analyzed. Additionally, the effect of these preparations on cell viability was evaluated using the MTT assay. Preparations with relatively high PCM concentrations showed a reduction in cell viability.