Gabriele Sadowski

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

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Publications (173)380.13 Total impact

  • 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.
    Molecular Pharmaceutics 06/2015; DOI:10.1021/mp500824d · 4.79 Impact Factor
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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.
    European journal of pharmaceutics and biopharmaceutics: official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V 06/2015; 94. DOI:10.1016/j.ejpb.2015.06.009 · 4.25 Impact Factor
  • 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.
    Journal of Chemical & Engineering Data 06/2015; DOI:10.1021/acs.jced.5b00175 · 2.05 Impact Factor
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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.
    Biotechnology and Bioengineering 05/2015; DOI:10.1002/bit.25655 · 4.16 Impact Factor
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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.
    Journal of Industrial Microbiology 04/2015; 42(7). DOI:10.1007/s10295-015-1621-x · 2.51 Impact Factor
  • 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.
    Industrial & Engineering Chemistry Research 04/2015; 54(15):150407161349002. DOI:10.1021/acs.iecr.5b00068 · 2.24 Impact Factor
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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.
    European journal of pharmaceutics and biopharmaceutics: official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V 03/2015; 93. DOI:10.1016/j.ejpb.2015.01.029 · 4.25 Impact Factor
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    ABSTRACT: To analyze the dissolution mechanism of solid dispersions of poorly water-soluble active pharmaceutical ingredients (APIs), to predict the dissolution profiles of the APIs and to find appropriate ways to improve their dissolution rate. The dissolution profiles of indomethacin and naproxen from solid dispersions in PVP K25 were measured in vitro using a rotating-disk system (USP II). A chemical-potential-gradient model combined with the thermodynamic model PC-SAFT was developed to investigate the dissolution mechanism of indomethacin and naproxen from their solid dispersions at different conditions and to predict the dissolution profiles of these APIs. The results show that the dissolution of the investigated solid dispersions is controlled by dissolution of both, API and PVP K25 as they codissolve according to the initial API loading. Moreover, the dissolution of indomethacin and naproxen was improved by decreasing the API loading in polymer (leading to amorphous solid dispersions) and increasing stirring speed, temperature and pH of the dissolution medium. The dissolution of indomethacin and naproxen from their amorphous solid dispersions is mainly controlled by the surface reaction, which implies that indomethacin and naproxen dissolution can be effectively improved by formulation design and by improving their solvation performance. The chemical-potential-gradient model combined with PC-SAFT can be used to analyze the dissolution mechanism of solid dispersions and to describe and predict the dissolution profiles of API as function of stirring speed, temperature and pH value of the medium. This work helps to find appropriate ways to improve the dissolution rate of poorly-soluble APIs.
    Pharmaceutical Research 02/2015; 32(8). DOI:10.1007/s11095-015-1644-z · 3.95 Impact Factor
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    ABSTRACT: In this work the electrolyte perturbed chain statistical associating fluid theory (ePC-SAFT) is applied to model aqueous two-phase systems (ATPS) containing one of 6 different polymers and one of 8 different organic salts at temperatures between 278.15 K and 313.15 K. To accurately model the thermodynamic properties of organic-salt solutions, a novel modeling approach was applied, which accounts for the non-spherical shape of the anions. Applying this approach, 14 organic salt solutions have been modeled with an overall average relative deviation of 0.23% for solution densities and 1.51% for osmotic coefficients. The modeling of the polymers (PEG, PEGDME, PPG, and poly(ethylene glycol-co-propylene glycol)) has been carried out using a copolymer approach accounting for different molecular interactions of the polymer segments. Applying this approach, ATPS containing polymers and organic salts were modeled accurately. The overall absolute average deviation of the modeling with respect to the concentrations of the phase-forming components was 2.10 wt%. The influence of polymer molecular weight, polymer composition, kind of salt, pH, and temperature on the equilibrium composition and densities of the two phases was modeled correctly with ePC-SAFT. Moreover, it is shown that by applying ion-specific model parameters, ePC-SAFT is even capable of predicting ATPS containing salts which were not used for the parameter estimation.
    Fluid Phase Equilibria 02/2015; 387:178-189. DOI:10.1016/j.fluid.2014.12.011 · 2.24 Impact Factor
  • Ole Riechert, Tim Zeiner, Gabriele Sadowski
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    ABSTRACT: This work presents a modeling approach using the Perturbed Chain-Statistical Associating Fluid Theory (PC-SAFT) for new liquid-liquid equilibria (LLE) data of ternary systems containing β-myrcene, acetonitrile, and n-alkanes, as well as binary mixtures thereof. The modeling approach is based on parameter estimations from binary systems and allows a general prediction of acetonitrile/n-alkane systems’ LLE and their ternary mixtures’ LLE with β-myrcene. The binary mixtures’ vapor-liquid equilibria (VLE) of β-myrcene with acetonitrile and n-alkanes were measured at 100 mbar. The ternary systems’ LLE were measured at ambient pressure and 298.15 K. Experimentally investigated alkanes are n-hexane, n-heptane, and n-octane. The approach was validated by successfully predicting the ternary system containing n-dodecane.
    Industrial & Engineering Chemistry Research 01/2015; 54(3):1153-1160. DOI:10.1021/ie502557g · 2.24 Impact Factor
  • Raphael Paus, Yuanhui Ji, Florian Braak, Gabriele Sadowski
    Industrial & Engineering Chemistry Research 01/2015; DOI:10.1021/ie503939w · 2.24 Impact Factor
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    ABSTRACT: In this work, Δ(R)g(+) values for the enzymatic G6P isomerization were determined as a function of the G6P equilibrium molality between 25°C and 37°C. The reaction mixtures were buffered at pH=8.5. In contrast to standard literature work, Δ(R)g(+) values were determined from activity-based equilibrium constants instead of molality-based apparent values. This yielded a Δ(R)g(+) value of 2.55±0.05kJmol(-1) at 37°C, independent of the solution pH between 7.5 and 8.5. Furthermore, Δ(R)h(+) was measured at pH=8.5 and 25°C yielding 12.05±0.2kJmol(-1). Accounting for activity coefficients turned out to influence Δ(R)g(+) up to 30% upon increasing the G6P molality. This result was confirmed by predictions using the thermodynamic model ePC-SAFT. Finally, the influence of the buffer and of potassium glutamate as an additive on the reaction equilibrium was measured and predicted with ePC-SAFT in good agreement.
    Biophysical Chemistry 12/2014; DOI:10.1016/j.bpc.2014.08.002 · 2.32 Impact Factor
  • Nikola Gushterov, Ferruccio Doghieri, Gabriele Sadowski
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    ABSTRACT: The high importance of natural rubber (NR) for mankind was identified already in the beginning of the 19th century. After the discovery of the vulcanization process, NR became one of the most significant renewable materials with an annual production of about 11 billion tons at present. Recently, the so-called shape-memory natural rubber (SMNR) was discovered [1]. SMNR is a lightly cross-linked NR, which can be used to store energy and very high strains. The shape-memory properties are received due to strain-induced crystallization, which occurs by stretching the polymer during a programming procedure. Programmed SMNR samples are thus semi-crystalline and can be triggered by mechanical force, heat and even through contact with VOC (volatile organic compound) vapors. Quitmann et al. [2] showed that constrained, lightly cross-linked SMNR even generates a reversible stress response upon exposure to VOC vapors, which depends on VOC type and concentration. This can be applied e.g. as vapor detector, as long as the mechanical reaction of the SMNR can be related to a certain VOC type and concentration. This requires the vapor-liquid-equilibrium (VLE) data of constrained SMNR/VOC systems. In this work, VLEs of constrained and unconstrained SMNR/VOC systems were investigated at 293.15 K using a magnetic suspension balance. The measurements provide VOC equilibrium concentrations and diffusivity data. The different strains correspond also to different initial polymer crystallinities, which show a notable effect on the VLEs. VLE modeling was performed using the Perturbed-Chain Statistical Associating Fluid Theory (PC‑SAFT). To account for the influence of constant strain on the VLE, a Helmholtz-energy contribution was used that accounts for network elasticity. This contribution is based on the affine network theory with a correction for the finite extensibility of the polymer chains [3]. The solubility of the VOCs in the amorphous part of the semi-crystalline SMNR was modeled based on the assumption that the crystalline phase does not absorb any solvent. The crystallinity of SMNR samples for each strain investigated was estimated based on literature data. Using the modeling approach suggested by Minelli and De Angelis [4], it was possible to correctly describe the experimental VLE data. For that purpose it was assumed that the crystallites exert an isotropic stress on the amorphous phase, which leads to reduced solubility in comparison to a non-stretched (fully amorphous) sample. This stress is quantified as an additional thermodynamic pressure inside the polymer phase and called constraint pressure pc. pc was considered as adjustable parameter. This allowed for quantitatively describing VLEs of SMNR/VOC systems over a broad range of strains and VOC concentrations. References [1] F. Katzenberg, B. Heuwers, J. C. Tiller, Adv. Mater., 2011, 23, 1909-1911. [2] D. Quitmann, N. Gushterov, G. Sadowski, F. Katzenberg, J. C. Tiller, ACS Appl. Mater. Interfaces, 2013, 5, 3504-3507. [3] B. Miao, T. A. Vilgis, S. Poggendorf, G. Sadowski, Macromol. Theory Simul., 2010, 19, 414-420. [4] M. Minelli, M. G. De Angelis, Fluid Phase Equilibria, 2014, 367, 173-181.
    14 AIChE Annual Meeting; 11/2014
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    ABSTRACT: Layer melt crystallization is a highly selective method for the separation of narrow boiling mixtures which are difficult to separate with conventional separation techniques like distillation due to low driving forces. Contrawise, layer melt crystallization has the drawback of limited capacity due to the direct connection between crystal product and required cooled surface. Here, the combination of the high throughput distillation and highly selective layer melt crystallization into an integrated hybrid process can lead to enormous benefits. Since the separation efficiency of the crystallization is not predictable, it has to be described with empirical correlation. Here, studies from literature use strongly simplified correlations by e.g. assuming complete separation. This bears the serious risk of overestimating the efficiency of the hybrid process. Further, the effective post purification step sweating was not implemented into hybrid processes in studies from literature. This study fills this gap in literature. A distilliation/melt crystallization hybrid process is optimized by realistically describing crystallization separation efficiency and by implementing sweating. The required crystallization models are presented and experimentally validated. The optimization of the hybrid process is done with different modelling depths and the results underline impressively the importance of the adequate description of the crystallization separation efficiency.
    Chemical Engineering and Processing 11/2014; DOI:10.1016/j.cep.2014.07.011 · 1.96 Impact Factor
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    ABSTRACT: The incorporation of poorly-soluble active pharmaceutical ingredients (APIs) into excipients (e.g. polymers) to formulate an amorphous solid dispersion is a promising strategy to improve the oral bioavailability of the API. The application of copolymer excipients allows access to combination of different monomers and thus to the design of excipients to improve solid-dispersion properties. In this work, the thermodynamic phase behavior of solid dispersions was investigated as function of API, type of monomers, and copolymer composition. The glass-transition temperatures and API solubilities in the solid dispersions of naproxen and indomethacin in polyvinyl pyrrolidone, polyvinyl acetate, and copolymers with different weight fractions of vinyl pyrrolidone and vinyl actetate were investigated. It could be shown that the thermodynamic phase behavior of API/copolymer solid dispersions is a function of monomer type and copolymer composition. This effect was also predicted by using the Perturbed-Chain Statistical Associating Fluid Theory (PC-SAFT). The glass-transition temperature of the solid dispersions was calculated with the Gordon-Taylor equation.
    Molecular Pharmaceutics 10/2014; 11(11). DOI:10.1021/mp500412d · 4.79 Impact Factor
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    I. Smirnova, G. Sadowski, S. Enders
    Chemie Ingenieur Technik 09/2014; 86(9). DOI:10.1002/cite.201450126 · 0.66 Impact Factor
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    C. Brandenbusch, C. Kress, G. Sadowski
    Chemie Ingenieur Technik 09/2014; 86(9). DOI:10.1002/cite.201450702 · 0.66 Impact Factor
  • Markus Christian Arndt, Gabriele Sadowski
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    ABSTRACT: The composition and swelling behaviour of hydrogels may be dramatically influenced by external stimuli. Polyelectrolyte hydrogels consisting of charged polymers are particularly well-known for a high sensitivity to the presence of ionic species. For a thermodynamic description of such systems, the pePC-SAFT equation of state was augmented and merged with an extension of the modelling of hydrogels. This combined approach allowed for two effects to be taken into account: first, charges along the polymer chain and their interaction with mobile ions of the same or opposite charge in aqueous solutions and, second, the elastic interactions of swellable networks and their effect on Helmholtz energy and pressure. Thus, predictions of the degree of counterion condensation on the polymer chains could be made for both vapour-liquid equilibria of aqueous polyelectrolyte solutions and for polyelectrolyte hydrogels in aqueous salt solutions. The influence of temperature and molecular weight thereon was predicted successfully, and the impact of the degree of neutralisation and the effect of additional salts were examined in comparison to literature data. With the inclusion of the influence of the Donnan potential, our model gave good predictions of swellable polyelectrolyte hydrogel systems in salt solutions. Poly (acrylic acid) and poly (methacrylic acid) gels were studied along with their corresponding sodium salts. Their swelling behaviour in aqueous NaCl and NaNO3 solutions was examined.
    The Journal of Physical Chemistry B 08/2014; 118(35). DOI:10.1021/jp501798x · 3.38 Impact Factor
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    ABSTRACT: In this work the electrolyte perturbed chain statistical associating fluid theory (ePC-SAFT) was applied to model aqueous two-phase systems (ATPS) containing combinations of polyethylene glycol dimethyl ether (PEGDME), polypropylene glycol (PPG) and three poly(ethylene glycol-co-propylene glycol) copolymers in combination with 12 different inorganic salts for temperatures ranging from 278 K to 333 K. For the polymer modeling, a copolymer approach was applied splitting the polymer in different segment types accounting for their different molecular interactions. Using this approach allows for quantitative modeling of phase properties of aqueous homopolymer and copolymer solutions. ATPS consisting of water, salt and one out of the five polymers were successfully modeled by using only one binary interaction parameter between each polymer segment type and each ion. Applying these parameter set, the influence of (co)polymer composition, polymer molecular weight, and temperature on the phase composition and phase densities could be modeled accurately.
    Fluid Phase Equilibria 08/2014; 375. DOI:10.1016/j.fluid.2014.04.040 · 2.24 Impact Factor
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    ABSTRACT: In reactive multiphase systems, the reactive phase can be manipulated not only by temperature and pressure, but also via coexisting "service" phases. For the exploitation of the full potential of such systems, a model-based reactor design that includes an accurate calculation of the equilibrium composition using advanced thermodynamic models is mandatory. This is of special importance when innovative solvent systems with complex phase behavior are considered. In this work, an equation based model containing reaction kinetics and an advanced equation of state, namely the perturbed-chain statistical associating fluid theory (PC-SAFT), was implemented for large-scale optimization. Exemplified on the hydroformylation of 1-octene it is demonstrated how such a model framework can be used as basis for optimal reactor design. After fitting the PC-SAFT parameters to pure component data the model was used to study the influence of product formation on the solubilities of H-2 and CO. Finally, the reaction conditions were optimized in order to maximize the differential selectivity to the desired product n-nonanal. It is shown that the performance of the hydroformylation reaction system can be significantly increased by optimally controlling temperature, total pressure, and the amount of H-2 and CO in the gas phase.
    Chemical Engineering Science 08/2014; 115:58-68. DOI:10.1016/j.ces.2013.03.051 · 2.61 Impact Factor

Publication Stats

3k Citations
380.13 Total Impact Points

Institutions

  • 2002–2015
    • 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