In this master's thesis, we aimed to establish a new method for estimating the impurity content of a model drug (ketoprofen) in the hot-melt extrusion (HME) process. Twenty-two formulations were prepared containing equal proportions of the model drug and a lubricant (Syloid® 244 FP) with different proportions of plasticizers (Parteck® M200, Polyglycol® 3350 P) and polymers. First, the glass transition temperature or melting point of all twenty-two blends was measured by differential scanning calorimetry (DSC) to determine the appropriate process temperature for subsequent extrusion on a single- and twin-screw extruder. In addition to the twenty-two samples extruded on the single-screw extruder, ten samples were extruded at 100 rpm and five samples at 300 rpm on the twin-screw extruder. The resulting extrudates were then analysed for ketoprofen and its impurities by high-performance liquid chromatography (HPLC). Meanwhile, the crystallinity of the drug was evaluated by tracking the melting peak of ketoprofen in DSC thermograms. In addition, we developed a DSC method that mimics the conditions during extrusion in a single- and twin-screw extruder for a small amount of the blend (⡈ 25 mg). To optimise the setup of the DSC method, the isothermal heating interval of the DSC and the gas composition of the calorimeter cell were first varied on a small number of formulations. In all experiments, the temperatures during isothermal heating always corresponded to the process temperatures during extrusion for each sample. Comparable impurity profiles of ketoprofen for single- and twin-screw extrudates were obtained using an average residence time with air atmosphere in the calorimeter cell. The results confirmed a very high degree of correlation between the impurities of ketoprofen in the treated powder blends and extrudates on the single-screw extruder (r=0.9600) and on the twin screw extruder (r=0.9879). The absence of a melting peak of ketoprofen in the thermograms of the extrudates suggests that ketoprofen is completely amorphized in the resulting solid dispersions. Our method provides an excellent starting point for developing a screening method to evaluate the suitability of formulations with different compositions for extrusion. Our method can be used to determine upper limits for extrusion temperature and melt residence time when establishing a »design space«. Both temperature and residence time affect the level of impurities, which is a critical parameter in production-level melt extrusion.
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