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

Drug Dev Ind Pharm. 2006 Jun;32(5):569-83. doi: 10.1080/03639040500528996.

Abstract

Controlled release tablets containing a poorly water-soluble drug, indomethacin (IDM), acrylic polymers (Eudragit RD 100, Eudragit L 100, or Eudragit 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 RL PO as demonstrated by a decrease in the glass transition temperatures of the polymer. The inclusion of either Pluronic F68, Eudragit L 100, or Eudragit S 100 in the powder blend containing Eudragit 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 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.

MeSH terms

  • Acrylic Resins / chemistry*
  • Adsorption
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
  • Anti-Inflammatory Agents, Non-Steroidal / chemistry
  • Calorimetry, Differential Scanning
  • Chemical Phenomena
  • Chemistry, Physical
  • Chromatography, High Pressure Liquid
  • Crystallization
  • Delayed-Action Preparations / chemistry*
  • Drug Compounding
  • Excipients
  • Hydrogen-Ion Concentration
  • Indomethacin / administration & dosage
  • Indomethacin / chemistry
  • Microscopy, Electron, Scanning
  • Particle Size
  • Pharmaceutical Preparations / administration & dosage*
  • Poloxamer / chemistry
  • Polymethacrylic Acids / chemistry
  • Solubility
  • Tablets
  • Thermogravimetry
  • X-Ray Diffraction

Substances

  • Acrylic Resins
  • Anti-Inflammatory Agents, Non-Steroidal
  • Delayed-Action Preparations
  • Excipients
  • Pharmaceutical Preparations
  • Polymethacrylic Acids
  • Tablets
  • Poloxamer
  • methylmethacrylate-methacrylic acid copolymer
  • Indomethacin