Controlled release of a poorly water-soluble drug from hot-melt extrudates containing acrylic polymers

Controlled release tablets containing a poorly water-soluble drug, indomethacin (IDM), acrylic polymers (Eudragit(R) RD 100, Eudragit(R) L 100, or Eudragit(R) S 100), and triethyl citrate (TEC) were prepared by hot-melt extrusion. The physicochemical and IDM release properties of the controlled release hot-melt extrudates were investigated. Indomethacin (IDM) was found to be both thermally and chemically stable following hot-melt extrusion processing and displayed a plasticizing effect on Eudragit(R) RL PO as demonstrated by a decrease in the glass transition temperatures of the polymer. The inclusion of either Pluronic(R) F68, Eudragit(R) L 100, or Eudragit(R) S 100 in the powder blend containing Eudragit(R) RD 100 prior to processing increased the rate of release of the IDM from the extrudates. An increase in the media pH and a decrease in the granule particle size also increased the rate of release of IDM. The inclusion of TEC up to 8% in the granule formulation or compressing the granules into tablets had no significant effect on the drug release rate. Indomethacin (IDM) was transformed from a crystalline Form I into an amorphous form in the Eudragit(R) RD 100 granules following hot-melt extrusion. The thermal processing facilitated the formation of a solid solution with a continuous matrix structure that was shown to control drug diffusion from the extrudates.