Properties of spherical pellets produced by a hot-melt extrusion and spheronization process

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Young, Christopher Ryan

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Melt-extrusion is an efficient, continuous and solvent-free process that has been studied to prepare granules, sustained-release tablets and transdermal drug delivery systems. The research in this dissertation investigated the physicochemical properties of spherical pellets produced by a novel melt- extrusion process. Pellets are widely employed in controlled-release systems. Wet-mass extrusion and spheronization is the more established method of producing spherical pellets, but this technique utilizes water and requires additional processing steps to produce controlled-release beads. Thus, a novel melt- extrusion technique was characterized to manufacture spherical pellets, and the controlled drug release properties of the resulting beads were examined. Furthermore, the physical properties of matrix pellets produced by either wet- mass or melt-extrusion were investigated, including morphology, porosity and particle size distribution. Although marketed controlled-release dosage forms exhibit significant differences in the design and composition, these preparations can be broadly categorized as single or multiple unit systems. Multiple unit dosage forms offer several advantages, such as improved bioavailability and reduced risks of dose dumping, local irritation and tampering. The physical and drug release properties of tablets compressed from melt-extruded pellets were investigated. Furthermore, the influences of compression force, filler excipient and pellet to excipient ratio on the properties of pellet containing compacts was investigated using drug release, hardness, friability and disintegration time determinations. The physicochemical properties of a melt-extruded system containing poly(ethylene oxide) and guaifenesin were studied. The calculated Hansen solubility parameters and thermal properties of materials were used to determine suitability of systems for thermal-processing. Following extrusion, the influence of accelerated storage conditions on the drug release and physical properties of pellets was studied. Furthermore, film-coating of melt-extruded beads with Eudragit® L 30 D-55 was studied to design a melt-extruded pellet system with pH-dependent drug release properties. Melt-extrusion processes were studied to manufacture controlled release matrix systems based on Acryl-EZE®, which is a pre-mixed excipient blend based on a methacrylic acid copolymer. The physical and chemical stability of materials during thermal processing was studied using thermal gravimetric analysis and HPLC. Modeling of drug release and swelling/erosion studies were employed to determine the influence of swelling agents on the mechanism and kinetics of drug release from thermally processed dosage forms.