Numerical simulation of five different screw configurations used during the preparation of hot-melt extruded Kollidon® and Soluplus® based amorphous solid dispersions containing indomethacin

Abstract

This work developed immediate-release hot melt extruded pellets containing the poorly aqueous soluble drug Indomethacin with five different screw configurations for oral application. Moreover, numerical simulation concerning residence time was performed for each configuration to give valuable tools for better process understanding and ease of scale-up. The pellets were prepared using immediate-release matrix-forming polymers such as Kollidon® and Soluplus® by coupling hot melt extrusion (HME) with a die-surface cutting pelletizer. The HME extruded filaments were pelletized with a die-surface cutting pelletizer into 1.5 mm pellets. The extruded pellets were characterized by differential scanning calorimetry (DSC), Fourier-transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM), in vitro release testing, drug content, and stability studies. DSC data revealed the formation of the amorphous solid dispersions of Indomethacin in both polymeric blends. FTIR spectra did not reveal any incompatibilities between the drug and the polymers. SEM micrographs revealed a smooth surface without any cracks. In vitro release studies demonstrated that the Indomethacin dissolution rate was significantly improved from both polymeric matrices for all the tested screw configurations compared to the bulk drug. However, the numerical simulation studies showed no significant difference between predicted and experimental extrusion residence time for only four screw configurations. In conclusion, the current investigation revealed the potential use of the continuous hot-melt extrusion technology for large-scale production of Indomethacin pellets with good prediction tools for the experimental extrusion residence time with standard, conveying, distributive, one mixing screw configurations for both polymers.