Combination of the PC-SAFT and FSC methods allows for accurate prediction of dipeptide solubility in water in a wide temperature range without the need to fit any model parameters to experimental solubility data.

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In downstream processes for peptides, crystallization is still used as the state-of-the-art separation step for which the knowledge about the solubility of each single compound is mandatory. Since the determination of experimental temperature-dependent solubility data is time-consuming and expensive, modeling solubility based on physical properties such as melting properties is highly desired. Unfortunately, the direct determination of melting properties for biomolecules using conventional differential scanning calorimetry is not possible due to the decomposition of the peptides before their melting. In this work, fast scanning calorimetry (FSC) with heating rates up to 20,000 K s–1 was applied to measure the melting properties of 22 peptides with focus on isomeric dipeptides and tripeptides based on glycine, l-alanine, l-leucine, l-proline, and l-serine. The experimental determination of the aqueous solubility of these peptides was performed using the photometric method (UV/Vis spectrometer) and the gravimetric method of supersaturated solutions. Additionally, the pH value and the crystal structure of peptides were determined in order to ensure the neutral species in solution and to exclude crystal structure changes in the solid phase. The experimental FSC-measured melting properties were used as input data in the thermodynamic modeling framework PC-SAFT to model the peptide solubility in water. The PC-SAFT pure-component parameters of the peptides were determined following a weighted joint-parameter method introduced in this work. This approach allows determining the pure-component parameters of a peptide by joining the pure-component parameters of the parent amino acids. The binary interactions parameter between peptide and water was fitted to solubility-independent properties such as osmotic coefficients and mixture densities of aqueous peptide solutions. The modeled peptide solubility was in good agreement with the experimental solubility.

Besides strict requirements for landfills the EU has also established criteria and procedures for the acceptance of waste delivered to landfills. Hazardous waste landfilled must meet the relevant waste acceptance criteria, which, besides standards for physical stability, consist of quantitative limits for leachable substances and organic matter. Evaluated testing methods -batch tests and a percolation test -were used in this investigation to study the leaching behaviour of oil shale semicoke. The results obtained indicate that none of the leaching limit values for inorganic components were exceeded in the analysed semicoke samples. The influence of recarbonation on the leachability of different components from semicoke was also studied.

The continuous vacuum screw filter (CVSF) for small-scale continuous product isolation of suspensions was operated for the first time with cuboid-shaped and needle-shaped particles. These high aspect ratio particles are very common in pharmaceutical manufacturing processes and provide challenges in filtration, washing, and drying processes. Moreover, the flowability decreases and undesired secondary processes of attrition, breakage, and agglomeration may occur intensively. Nevertheless, in this study, it is shown that even cuboid and needle-shaped particles (l-alanine) can be processed within the CVSF preserving the product quality in terms of particle size distribution (PSD) and preventing breakage or attrition effects. A dynamic image analysis-based approach combining axis length distributions (ALDs) with a kernel-density estimator was used for evaluation. This approach was extended with a quantification of the center of mass of the density-weighted ALDs, providing a measure to analyze the preservation of the inlet PSD statistically. Moreover, a targeted residual moisture below 1% could be achieved by adding a drying module (Tdry = 60 °C) to the modular setup of the CVSF.

Integrated continuous manufacturing processes of active pharmaceutical ingredients (API) provide key benefits concerning product quality control, scale-up capability, and a reduced time-to-market. Thereby, the crystallization step, which is used in approximately 90% of API productions, mainly defines the final API properties. This study focuses on the design and operation of an integrated small-scale process combining a continuous slug flow crystallizer (SFC) with continuous particle isolation using the modular continuous vacuum screw filter (CVSF). By selective adjustment of supersaturation and undersaturation, the otherwise usual blocking could be successfully avoided in both apparatuses. It was shown that, during crystallization in an SFC, a significant crystal growth of particles (Δd50,3≈ 220 µm) is achieved, and that, during product isolation in the CVSF, the overall particle size distribution (PSD) is maintained. The residual moistures for the integrated process ranged around 2% during all experiments performed, ensuring free-flowing particles at the CVSF outlet. In summary, the integrated setup offers unique features, such as its enhanced product quality control and fast start-up behavior, providing a promising concept for integrated continuous primary manufacturing processes of APIs.

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