Stability studies of hot-melt extruded ternary solid dispersions of poorly-water soluble Indomethacin with Poly(vinyl pyrrolidone-co-vinyl acetate) and polyethylene oxide.

Abstract

This investigation aims to evaluate the effect of moisture and temperature on the physical stability and dissolution behaviour of hot-melt extruded binary and plasticised ternary solid dispersions. Poorly water-soluble indomethacin (IND), poly(vinyl pyrrolidone-co-vinyl acetate) (PVPVA) and plasticiser polyethylene oxide (PEO) were selected as model compounds. Extruded samples were stored with 40 °C, at 0 % and 75 % relative humidity (RH) for 12 weeks. Results confirmed that binary solid dispersions of PVPVA-IND were successfully prepared by twin-screw hot-melt extrusion producing amorphous single-phase systems. The inclusion of semi-crystalline PEO reduced the melt viscosity of the system acting as a processing aid during extrusion without modifying the glass transition temperature (Tg) of the final doses. Samples stored at low humidity levels exhibited a dissolution profile similar to the unannealed dispersions. Samples annealed at 75 % RH showed a decrease in the dissolution rate, likely related to phase separation due to the increase in molecular mobility after the water sorption. However, all the annealed samples showed a total release of IND, indicating that the dispersions were relatively stable up to 12 weeks.