Effects of extrusion process parameters on the dissolution behavior of indomethacin in Eudragit E PO solid dispersions.

This work studied the dissolution of indomethacin (INM) into polymer excipient Eudragit E PO (E PO) melt at temperatures lower than the melting point of INM using a laboratory-size, twin-screw counter-rotating batch internal mixer. The effects of three process parameters--set mixer temperature, screw rotating speed and residence time--were systematically studied. Scanning electron microscopy (SEM), optical microscopy (OM), X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FT-IR) were employed to investigate the evolution of INM's dissolution into the molten excipient. Differential scanning calorimetry (DSC) was used to quantitatively study the melting enthalpy evolution of the drug. The results showed that the dissolution rate increased with increasing the mixer set temperature, or the screw rotating speed. It was concluded that the dissolution of the drug in the polymer melt is a convective diffusion process, and that laminar distributive mixing can significantly enhance the dissolution rate. More importantly, the time needed for the drug to dissolve inside the molten polymer and the typical residence time for an extrusion process fall in the same range.