Gabriele Sadowski

Technische Universität Dortmund, Dortmund, North Rhine-Westphalia, Germany

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Publications (197)423.32 Total impact

  • Lawien F Zubeir · Christoph Held · Gabriele Sadowski · Maaike C. Kroon
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    ABSTRACT: Perturbed-Chain Statistical Associating Fluid Theory (PC-SAFT), a physically based model that accounts for different molecular interactions explicitly, was applied to describe for the first time the phase behavior of deep eutectic solvents (DESs) with CO2 at temperatures from 298.15 to 318.15 K and pressures up to 2 MPa. DESs are mixtures of two solid compounds, a hydrogen bond donor (HBD) and a hydrogen bond acceptor (HBA), which form liquids upon mixing with melting points far below that of the individual compounds. In this work, the HBD is lactic acid and the HBAs are tetramethylammonium chloride, tetraethylammonium chloride and tetrabutylammonium chloride. Two different modeling strategies were considered for the PC-SAFT modeling. In the first strategy, the so-called pseudo-pure component approach, a DES was considered as a pseudo-pure compound, and its pure-component parameters were obtained by fitting to pure DES density data. In the second strategy, the so-called individual-component approach, a DES was considered to consist of two individual components (HBA and HBD), and the pure-component parameters of the HBA and HBD were obtained by fitting to the density of aqueous solutions containing only the individual compounds of the DES. In order to model vapor-liquid equilibria (VLE) of DES + CO2 systems, binary interaction parameters were adjusted to experimental data from literature and to new data measured in this work. It was concluded that the individual-component strategy allows quantitatively prediction of the phase behavior of DES + CO2 systems containing those HBD:HBA molar ratios that were not used for kij fitting. In contrast, applying the pseudo-pure component strategy required DES-composition specific kij parameters.
    No preview · Article · Jan 2016 · The Journal of Physical Chemistry B
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    ABSTRACT: In this work we applied experimental and theoretical thermodynamics to methyl ferulate hydrolysis, a model biological reaction in order to calculate the equilibrium constant and reaction enthalpy. In the first step, reaction data was collected. Temperature-dependent equilibrium concentrations of methyl ferulate hydrolysis have been measured. These were combined with activity coefficients predicted with electrolyte PC-SAFT in order to derive thermodynamic equilibriums constants Ka as a function of temperature.
    No preview · Article · Jan 2016 · Fluid Phase Equilibria
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    ABSTRACT: The thermodynamic equilibrium of the aminotransferase reaction from L-alanine and 2-oxoglutarate to L-glutamate and pyruvate in aqueous solution was investigated in a temperature range between 25 and 37 °C and pH between at 5 and 9.
    No preview · Article · Jan 2016 · Fluid Phase Equilibria
  • Marcel Herhut · Christoph Brandenbusch · Gabriele Sadowski
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    ABSTRACT: The development of a precipitation or crystallization step requires knowing the solubility of the target protein and its crystallization behavior in aqueous solutions at different pH, temperatures and in the presence of precipitating agents, especially salts. Within this work, a solubility model for proteins based on the second osmotic virial coefficient B22 is developed. For this, a relation between protein solubility and B22 was combined with the extended DLVO model. This solubility model was then used to model and also predict the protein solubility of lysozyme and monoclonal antibody for different salts, salt concentrations, and pH. The modeled as well predicted B22 and protein solubility data of lysozyme in the presence of sodium chloride and sodium p-toluenesulfonate and of a monoclonal antibody in the presence of ammonium sulfate at different pH shows good agreement with experimental data.
    No preview · Article · Jan 2016 · Fluid Phase Equilibria
  • Marcel Herhut · Christoph Brandenbusch · Gabriele Sadowski
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    ABSTRACT: Protein purification is often performed using cost-intensive chromatographic steps. To discover economic alternatives (e.g., crystallization), knowledge on protein solubility as a function of temperature, pH, and additives in solution as well as their concentration is required. State-of-the-art models for predicting protein solubility almost exclusively consider aqueous salt systems, whereas 'salting-in' and 'salting-out' effects induced by the presence of an additional polymer are not considered. Thus, we developed the sol-mxDLVO model. Using this newly developed model, protein solubility in the presence of one salt and one polymer, especially the non-monotonic course of protein solubility, could be predicted. Systems considered included salts (NaCl, Na-p-Ts, (NH(4) )(2) SO(4) ) and the polymer polyethylene glycol (MW: 2000 g/mol, 12000 g/mol) and proteins lysozyme from chicken egg white (pH 4 to 5.5) and D-xylose ketol-isomerase (pH 7) at 298.15 K. The results show that by using the sol-mxDLVO model, protein solubility in polymer-salt solutions can be modeled in good agreement with the experimental data for both proteins considered. The sol-mxDLVO model can describe the non-monotonic course of protein solubility as a function of polymer concentration and salt concentration, previously not covered by state-of-the-art models.
    No preview · Article · Nov 2015 · Biotechnology Journal
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    ABSTRACT: In biotechnological processes, salts might be present during reaction steps and in downstream processes. Salts are known to have a strong impact on phase equilibria of aqueous systems.
    No preview · Article · Nov 2015 · Fluid Phase Equilibria
  • Ole Riechert · Maik Husham · Gabriele Sadowski · Tim Zeiner
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    ABSTRACT: Solvents are known to have strong impacts on the yields of equilibrium reactions. This work focuses on the thermodynamic investigation of these solvent effects on esterification reactions of acetic acid and propionic acid with ethanol. Esterification of acetic acid was performed in the solvents acetone, acetonitrile (ACN), dimethylformamide (DMF), and tetrahydrofurane as well as in mixtures thereof. ACN promotes the esterification of acetic acid, whereas it is strongly suppressed by DMF. The esterification of propionic acid was investigated with various reactant concentrations in acetone. The experimental equilibrium data in pure solvents and solvent mixtures were modeled using the thermodynamic equilibrium constant Ka and the reactant/product activity coefficients predicted by the perturbed chain-statistical associating fluid theory (PC-SAFT). For a given Ka, PC-SAFT is able to predict the influence of the solvent and even solvent mixtures on the equilibrium concentrations of esterification in almost quantitative agreement with the experimental data. © 2015 American Institute of Chemical Engineers AIChE J, 61: 3000–3011, 2015
    No preview · Article · Sep 2015 · AIChE Journal
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    ABSTRACT: The homogeneously catalysed hydroamination reaction of β-myrcene with morpholine to terpenyl amines was investigated. Two different techniques to avoid catalyst losses from the liquid phase were applied: Thermomorphic Multicomponent Solvent (TMS)-systems, in which the temperature-sensitivity of the binodal curve is exploited and Liquid-Liquid Two-Phase (LLTP)-systems, in which the reaction happens at the phase interface. The highest β-myrcene conversion of more than 90% and a product yield of more than 80% was measured in a TMS-system consisting of n-heptane and acetonitrile. The same conversion was reached in a LLTP-system consisting of water and β-myrcene, whereas a product yield of 55% was achieved. Experimental data of the liquid-liquid phase equilibria resulted in thermodynamic fundamentals for the design of chemical reactors for the production of amines. Theoretical prediction of equilibrium compositions using PC-SAFT equation of state agree excellent with measured values.
    No preview · Article · Sep 2015 · Chemical Engineering and Processing
  • Marcel Herhut · Christoph Brandenbusch · Gabriele Sadowski
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    ABSTRACT: The downstream processing of therapeutic proteins is a challenging task. Key information needed to estimate applicable workup strategies (e.g. crystallization) are the interactions of the proteins with other components in solution. This information can be deduced from the second osmotic virial coefficient, B22 , measurable by static light scattering. Thermodynamic models are very valuable for predicting B22 data for different process conditions and thus decrease the experimental effort. Available B22 models consider aqueous salt solutions but fail for the prediction of B22 if an additional polymer is present in solution. This is due to the fact that depending on the polymer concentration protein-protein interactions are not rectified as assumed within these models. In this work, we developed an extension of the xDLVO model to predict B22 data of proteins in aqueous polymer-salt solutions. To show the broad applicability of the model, lysozyme, γ globulin and D-xylose ketol isomerase in aqueous salt solution containing polyethylene glycol were considered. For all proteins considered, the modified xDLVO model was able to predict the experimentally observed non-monotonical course in B22 data with high accuracy. When used in an early stage in process development, the model will contribute to an efficient and cost effective downstream processing development. Copyright © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
    No preview · Article · Aug 2015 · Biotechnology Journal
  • Linda Lange · Gabriele Sadowski
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    ABSTRACT: The purpose of this work is to increase the efficiency of the cocrystal formation process by thermodynamic modeling using perturbed-chain statistical associating fluid theory (PC-SAFT). By accounting for the thermodynamic nonideality of the components in the cocrystal system, PC-SAFT is able to model and predict the solubility behavior of pharmaceutical cocrystals based solely on the knowledge of a single cocrystal solubility point in any solvent and at any temperature. Furthermore, the cocrystal solubility in other solvents and for other temperatures can be predicted without the need for additional measurements. The (+)-mandelic acid/(-)-mandelic acid (1:1), caffeine/glutaric acid (1:1), and carbamazepine/nicotinamide (1:1) cocrystal systems were modeled, and the results were in excellent agreement with the experimental data. (Figure Presented).
    No preview · Article · Jul 2015 · Crystal Growth & Design
  • Raphael Paus · Elena Hart · Yuanhui Ji · Gabriele Sadowski
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    ABSTRACT: The solubility of cinnarizine has been investigated in acetonitrile, butyl acetate, 1-butanol, 2-propanol, and water in a temperature range from 288.15 K to 313.15 K. During crystallization from these solvents two different crystal morphologies of cinnarizine were observed. The caloric properties (melting temperature, melting enthalpy, and the difference in the heat capacity of solid and liquid cinnarizin) were measured by differential scanning calorimetry. The temperature-dependent solubility of cinnarizine in different organic solvents and in water was modeled using the perturbed-chain statistical associating fluid theory and was in good agreement with the experimental data.
    No preview · Article · Jul 2015 · Journal of Chemical & Engineering Data
  • Christoph Held · Gabriele Sadowski
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    ABSTRACT: Organisms developed very different strategies to protect themselves against osmotic stress. To sustain high salt concentrations of their surrounding some organisms accumulate so-called compatible solutes (CSs), which increase the internal osmotic pressure without disturbing the organism's metabolism. At constant temperature, osmotic pressure is mainly determined by the concentration of the compatible solute and the osmotic coefficient of the aqueous solution, and to a minor extent also by solution densities. Thus, osmotic coefficients and densities were measured for aqueous CS solutions in a broad range of concentration and at three temperatures (273. K, 310. K, 323. K) at atmospheric pressure. Further, the solubility of CSs in water was measured as function of temperature to determine the maximum CS concentration that can be applied in aqueous solutions. CSs under investigation were trimethylamine N-oxide (TMAO), trehalose, citrulline, N,. N-dimethylglycine, DMSO, glycerol, methylglycine, and ectoine. The data was used to calculate real osmotic pressures induced by these CSs. PC-SAFT was applied to model thermodynamic properties and phase equilibria of aqueous CS solutions in quantitative agreement to experimental data. Among the CSs investigated in this work, TMAO induced the highest osmotic pressure and thus can be considered the best protector against osmotic stress. The data was finally analyzed concerning the influence of CSs molecular size, charge, and hydrophobicity on osmotic pressure. This included also the comparison to incompatible solutes (urea, glycine).
    No preview · Article · Jul 2015 · Fluid Phase Equilibria
  • Anke Prudic · Yuanhui Ji · Christian Luebbert · Gabriele Sadowski
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    ABSTRACT: Amorphous formulations of APIs in polymers tend to absorb water from the atmosphere. This absorption of water can induce API recrystallization, leading to reduced long-term stability during storage. In this work, the phase behavior of different formulations was investigated as a function of relative humidity. Indomethacin and naproxen were chosen as model APIs and poly(vinyl pyrrolidone) (PVP) and poly(vinyl pyrrolidone-co-vinyl acetate) (PVPVA64) as excipients. The formulations were prepared by spray drying. The water sorption in pure polymers and in formulations was measured at 25°C and at different values of relative humidity (RH = 25%, 50% and 75%). Most water was absorbed in PVP-containing systems, and water sorption was decreasing with increasing API content. These trends could also be predicted in good agreement with the experimental data using the thermodynamic model PC-SAFT. Furthermore, the effect of absorbed water on API solubility in the polymer and on the glass-transition temperature of the formulations was predicted with PC-SAFT and the Gordon-Taylor equation, respectively. The absorbed water was found to significantly decrease the API solubility in the polymer as well as the glass-transition temperature of the formulation. Based on a quantitative modeling of the API/polymer phase diagrams as function of relative humidity, appropriate API/polymer compositions can now be selected to ensure long-term stable amorphous formulations at given storage conditions. Copyright © 2015. Published by Elsevier B.V.
    No preview · Article · Jun 2015 · European journal of pharmaceutics and biopharmaceutics: official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V
  • Raphael Paus · Yuanhui Ji · Lisa Vahle · Gabriele Sadowski
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    ABSTRACT: To improve the solubility and bioavailability of poorly-soluble active pharmaceutical ingredients (APIs), the transformation of crystalline APIs into the amorphous state has often been shown to be advantageous. As it is often difficult to measure the solubility of amorphous APIs, the application of thermodynamic models is the method of choice for determining the solubility advantage. In this work, the temperature-dependent solubility advantage of an amorphous API versus its crystalline form was predicted for five poorly-soluble APIs in water (glibenclamide, griseofulvin, hydrochlorothiazide, indomethacin and itraconazole) based on modeling the API/solvent phase diagrams using the Perturbed-Chain Statistical Associating Fluid Theory (PC-SAFT). To evaluate the performance of this approach, the predicted solubility advantage was compared to experimental data and to the solubility advantage calculated by the commonly-applied Gibbs-energy-difference method. For all systems considered, PC-SAFT predictions of the solubility advantage are significantly more accurate than the results obtained from the Gibbs-energy-difference method.
    No preview · Article · Jun 2015 · Molecular Pharmaceutics
  • Ole Riechert · Tim Zeiner · Gabriele Sadowski
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    ABSTRACT: This work presents investigations on the liquid-liquid equilibria (LLE) of ternary systems composed of morpholine, acetonitrile, and an n-alkane at 298.15 K and atmospheric pressure. The investigated n-alkanes were n-hexane, n-heptane, and n-octane. The experimental data were compared to predictions using the perturbed chain-statistical associating fluid theory (PC-SAFT). The predictions are based on pure-component parameters fitted to vapor pressures and liquid densities as well as on binary parameters fitted to binary systems’ phase equilibria. For that purpose, the vapor-liquid equilibrium of the morpholine/acetonitrile system was measured at 100 mbar and modeled with PC-SAFT. Binary interaction parameters for acetonitrile/n-alkane systems were obtained from a correlation as a function of the n-alkane carbon number. This correlation, together with the other pure-component and binary parameters, was used to make predictions on ternary systems with n-alkanes longer than n-octane, for which data were taken from literature. All ternary LLE predictions were in satisfactory agreement with experimental data.
    No preview · Article · Jun 2015 · Journal of Chemical & Engineering Data
  • Peng Ke · Sheng Qi · Gabriele Sadowski · Defang Ouyang
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    ABSTRACT: Drugs contained in solid oral dosage forms need to have good solubility in order to result in good bioavailability provided they also have good permeability. Recently, controlled release systems utilize solid dispersion technology to achieve an extended release profile of poorly water-soluble drugs with a short biological half-life. There are two main methods for the preparation of solid dispersions: one is through the use of a liquid phase such as melting and solvent methods, and the other is through a solid phase such as mechanical methods. Ball milling has been widely used to make the amorphous phase. Factors which can affect the physical stability of amorphous solid dispersions have been investigated widely, and glass transition temperatures (Tg), molecular mobility, physical stability of amorphous drugs alone, miscibility between drugs and polymers, and solid solubility of drugs in polymers have been considered as key factors influencing the physical stability of solid dispersions.
    No preview · Chapter · May 2015
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    ABSTRACT: The formation of stable emulsions in biphasic biotransformations catalyzed by microbial cells turned out to be a major hurdle for industrial implementation. Recently, a cost-effective and efficient downstream-processing approach, using supercritical carbon dioxide (scCO2 ) for both irreversible emulsion destabilization (enabling complete phase separation within minutes of emulsion treatment) and product purification via extraction has been proposed by Brandenbusch et al.(Biotechnology and Bioengineering 107:642-651, 2010). One of the key factors for a further development and scale-up of the approach is the understanding of the mechanism underlying scCO2 -assisted phase separation. A systematic approach was applied within this work to investigate the various factors influencing phase separation during scCO2 treatment (that is pressure, exposure of the cells to CO2 , and changes of cell surface properties). It was shown that cell toxification and cell disrupture are not responsible for emulsion destabilization. Proteins from the aqueous phase partially adsorb to cells present at the aqueous-organic interface, causing hydrophobic cell surface characteristics, and thus contribute to emulsion stabilization. By investigating the change in cell-surface hydrophobicity of these cells during CO2 treatment, it was found that a combination of catastrophic phase inversion and desorption of proteins from the cell surface is responsible for irreversible scCO2 mediated phase separation. These findings are essential for the definition of process windows for scCO2 -assisted phase separation in biphasic whole-cell biocatalysis. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    No preview · Article · May 2015 · Biotechnology and Bioengineering
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    ABSTRACT: Emulsion stability plays a crucial role for mass transfer and downstream processing in organic-aqueous bioprocesses based on whole microbial cells. In this study, emulsion stability dynamics and the factors determining them during two-liquid phase biotransformation were investigated for stereoselective styrene epoxidation catalyzed by recombinant Escherichia coli. Upon organic phase addition, emulsion stability rapidly increased correlating with a loss of solubilized protein from the aqueous cultivation broth and the emergence of a hydrophobic cell fraction associated with the organic-aqueous interface. A novel phase inversion-based method was developed to isolate and analyze cellular material from the interface. In cell-free experiments, a similar loss of aqueous protein did not correlate with high emulsion stability, indicating that the observed particle-based emulsions arise from a convergence of factors related to cell density, protein adsorption, and bioreactor conditions. During styrene epoxidation, emulsion destabilization occurred correlating with product-induced cell toxification. For biphasic whole-cell biotransformations, this study indicates that control of aqueous protein concentrations and selective toxification of cells enables emulsion destabilization and emphasizes that biological factors and related dynamics must be considered in the design and modeling of respective upstream and especially downstream processes.
    No preview · Article · Apr 2015 · Journal of Industrial Microbiology
  • Franziska Laube · Timo Klein · Gabriele Sadowski
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    ABSTRACT: Liquid-liquid extraction is a potential separation process for the purification of active pharmaceutical ingredients (APIs). The design of an extraction step requires knowledge of the API partition coefficient, which strongly depends on the solvent system and process conditions. Usually, cost-intensive experiments have to be performed to select the most suitable solvent system and the best process conditions. The number of experiments can be reduced by predicting the partition coefficient using PC-SAFT (Perturbed Chain Statistical Associating Theory). In this work, the modeling results and experimental data were compared for the partition coefficients of the APIs nicotinamide and salicylamide in different solvent systems at temperatures from 293.15 K to 328.15 K and at pHs varying between 5.2 and 10.3. The results show that PC-SAFT is able to predict the API partition coefficients for different solvent systems as functions of temperature and pH.
    No preview · Article · Apr 2015 · Industrial & Engineering Chemistry Research
  • Anke Prudic · Anna-Katharina Lesniak · Yuanhui Ji · Gabriele Sadowski
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    ABSTRACT: In the current study, the phase behaviour of indomethacin and poly(lactic-co-glycolic acid) (PLGA) formulations was investigated as a function of the molecular weight and the copolymer composition of PLGA. The formulations were prepared by ball milling, and the phase behaviour, comprised of the glass-transition temperature of the formulations and the solubility of indomethacin in PLGA, was measured using modulated differential scanning calorimetry (mDSC). The results determined that the solubility of indomethacin in PLGA at room temperature was very low and increased with a corresponding decrease in the molecular weight of PLGA. The copolymer composition of PLGA had a minor effect on the indomethacin solubility. The effect of PLGA's molecular weight and copolymer composition on the solubility of indomethacin could be modelled using the Perturbed-Chain Statistical Associating Fluid Theory (PC-SAFT) with a high degree of accuracy when compared with the experimental data. The glass-transition temperatures had a negative deviation from the weighted mean of the glass-transition temperatures of the pure substances, which could be described by the Kwei-equation. Copyright © 2015. Published by Elsevier B.V.
    No preview · Article · Mar 2015 · European journal of pharmaceutics and biopharmaceutics: official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V

Publication Stats

4k Citations
423.32 Total Impact Points

Institutions

  • 2001-2016
    • Technische Universität Dortmund
      • Laboratory of Thermodynamics (TH)
      Dortmund, North Rhine-Westphalia, Germany
  • 2012
    • Johannes Gutenberg-Universität Mainz
      • Institute of Physics
      Mayence, Rheinland-Pfalz, Germany
  • 2007
    • Saint Petersburg State University
      Sankt-Peterburg, St.-Petersburg, Russia
  • 1995-2003
    • Technische Universität Berlin
      • Institut für Prozess- und Verfahrenstechnik
      Berlín, Berlin, Germany