Properties of drug-containing spherical pellets produced by a hot-melt extrusion and spheronization process.
The objectives of this study were to investigate the particle size distribution, morphology and dissolution properties of spherical pellets produced by hot-melt extrusion and spheronization and to compare the properties of hot-melt extruded pellets with beads manufactured by a traditional wet-mass extrusion and spheronization method. Spherical pellets were produced by hot-melt extrusion without the use of water or other solvents. A powder blend of theophylline, Eudragit Preparation 4135 F, microcrystalline cellulose and polyethylene glycol 8000 was hot melt-extruded and the resulting composite rod was cut into cylindrical pellets. The pellets were then spheronized in a traditional spheronizer at an elevated temperature. The same powder blend was processed using conventional wet-mass techniques. Unlike wet-mass extruded pellets, pellets prepared from hot-melt extrusion displayed both a narrow particle size distribution and controlled drug release in dissolution media less than pH 7.4. Scanning electron microscopy, X-ray diffraction and porosity measurements were employed to explain the differences in drug release rates of theophylline from pellets produced by the two processing techniques. Theophylline release from the hot-melt extruded pellets was described using the Higuchi diffusion model, and drug release rates from wet-granulated and melt-extruded pellets did not change after post-processing thermal treatment.
Young
C R
CR
Drug Dynamics Institute, College of Pharmacy, The University of Texas at Austin, 78712, USA. chris.young@mail.utexas.edu
Koleng
J J
JJ
McGinity
J W
JW
D001672:Biocompatible Materials; D002482:Cellulose; D003692:Delayed-Action Preparations; D004058:Diffusion; D004339:Drug Compounding / Q000379:methods*; D004343:Drug Implants; D005782:Gels; D006358:Hot Temperature; D006863:Hydrogen-Ion Concentration; D008855:Microscopy, Electron, Scanning / Q000379:methods; D010316:Particle Size; D011092:Polyethylene Glycols; D011109:Polymethacrylic Acids; D016062:Porosity; D013806:Theophylline; D014961:X-Ray Diffraction / Q000379:methods
D001672:Biocompatible Materials; D003692:Delayed-Action Preparations; D004343:Drug Implants; D005782:Gels; D011109:Polymethacrylic Acids; C038300:methylmethacrylate-methacrylic acid copolymer; D011092:Polyethylene Glycols; D002482:Cellulose; D013806:Theophylline