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 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.
Zhu
Yucun
Y
Solid Dose R&D, Kos Pharmaceuticals Inc., 2 Oakwood Boulevard, Hollywood, FL 33020, USA. yuzhu@kospharm.com
Shah
Navnit H
NH
Malick
A Waseem
AW
Infeld
Martin H
MH
McGinity
James W
JW
D000180:Acrylic Resins / Q000737:chemistry*; D000327:Adsorption; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000737:chemistry; D002152:Calorimetry, Differential Scanning; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002851:Chromatography, High Pressure Liquid; D003460:Crystallization; D003692:Delayed-Action Preparations / Q000737:chemistry*; D004339:Drug Compounding; D005079:Excipients; D006863:Hydrogen-Ion Concentration; D007213:Indomethacin / Q000008:administration & dosage / Q000737:chemistry; D008855:Microscopy, Electron, Scanning; D010316:Particle Size; D004364:Pharmaceutical Preparations / Q000008:administration & dosage*; D020442:Poloxamer / Q000737:chemistry; D011109:Polymethacrylic Acids / Q000737:chemistry; D012995:Solubility; D013607:Tablets; D013818:Thermogravimetry; D014961:X-Ray Diffraction
D000180:Acrylic Resins; D000894:Anti-Inflammatory Agents, Non-Steroidal; D003692:Delayed-Action Preparations; D005079:Excipients; D004364:Pharmaceutical Preparations; D011109:Polymethacrylic Acids; D013607:Tablets; D020442:Poloxamer; C038300:methylmethacrylate-methacrylic acid copolymer; D007213:Indomethacin