Controlled Release Solid Dosage Forms by Melt-Extrusion (English shop)

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Melt extrusion represents a promising manufacturing technique for solid oral dosage forms with controlled drug release, although its pharmaceutical application is limited by the availability of suitable excipients. This dissertation investigates different matrix-forming materials for melt extrusion and evaluates their influence on drug release characteristics and formulation performance. Four pharmaceutical excipients are examined: glyceryl dibehenate (GDB), glyceryl palmitostearate (GPS), sucrose stearate (SUS), and hydroxypropyl cellulose (HPC). Theophylline is selected as a model drug and incorporated into the respective matrices at drug loadings of 25%, 50%, and 75%. Experimental investigations focus on extrusion processing conditions, granule characterization, powder flow properties, deformation behavior, and tablet compression performance. X-ray diffraction analysis confirms that theophylline remains predominantly crystalline following the melt-extrusion process. The investigated matrices provide a broad range of release profiles, with GDB and GPS controlling drug release for more than 20 hours, whereas SUS formulations achieve complete release within approximately 10 to 12 hours. HPC matrices containing low drug concentrations provide faster release, with complete liberation occurring within six hours. Further investigations examine the effects of drug loading, dissolution medium pH, ionic strength, storage stability, and hydrodynamic conditions on release kinetics. Particular attention is devoted to food-induced changes in drug release and the contribution of diffusion- and erosion-controlled mechanisms. A modified dissolution testing method is employed to investigate potential food effects, followed by in vivo studies in dogs to evaluate the predictive performance of the experimental approach. The findings demonstrate promising correlations between selected in vitro experiments and drug release under fasted conditions, while accurately predicting release in the fed state requires further methodological refinement. Overall, the dissertation contributes to the development and optimization of melt-extruded controlled-release dosage forms and provides insights into the relationship between matrix composition, manufacturing conditions, and pharmaceutical performance.