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Prof. Dr. Gabriele Sadowski is full Professor for Thermodynamics at TU Dortmund University. She received her PhD in Physical Chemistry afterwards became Associate Professor at TU Berlin. In 2001, she became full professor in Dortmund. She is author of more than 250 scientific papers in the field of chemical, biochemical, and pharmaceutical engineering. The main focus of her research is studying thermodynamic properties of complex systems with particular emphasis to those containing pharmaceutical molecules. Her group developed the currently worldwide most-used thermodynamic model PC-SAFT. She received numerous awards for her work, the most prestigious one being the Gottfried Wilhelm Leibniz Award of the German Science Foundation in 2011. In 2020, she was awarded the Distinguished Lecture in Thermodynamic and Transport Properties from the European Federation of Chemical Engineering. She is member the Academy of Science and Arts of Nordhrein-Westfalia and of the German Academy of Technical Sciences acatech.
Knowing the solubilities of active pharmaceutical ingredients (APIs) in pure solvents and solvent mixtures is essential for several manufacturing aspects of pharmaceutical product development. In this paper, we demonstrate that time-consuming and costly experiments can be reduced to a minimum using the thermodynamic model Perturbed-Chain Statistical Associating Fluid Theory (PC-SAFT) that can simultaneously predict API solubilities in pure solvents and solvent mixtures as well as unwanted liquid-liquid phase separation (LLPS). We investigated the temperature-dependent solubility of naproxen, ritonavir, and indomethacin in the solvents acetone, dichloromethane, ethanol, ethyl acetate, methanol, 2-propanol, tetrahydrofuran, and water, and mixtures thereof. Solvent mixtures with predicted enhanced API solvation properties (cosolvency) were validated by experiments. Moreover, concentration regions in which LLPS was predicted to occur were also found to be in perfect agreement with the experimental data.
Stefanie Dohrn; Christian Luebbert; Kristin Lehmkemper; Samuel O. Kyeremateng; Matthias Degenhardt; Gabriele Sadowski. Solvent mixtures in pharmaceutical development: Maximizing the API solubility and avoiding phase separation. Fluid Phase Equilibria 2021, 548, 113200 .
AMA StyleStefanie Dohrn, Christian Luebbert, Kristin Lehmkemper, Samuel O. Kyeremateng, Matthias Degenhardt, Gabriele Sadowski. Solvent mixtures in pharmaceutical development: Maximizing the API solubility and avoiding phase separation. Fluid Phase Equilibria. 2021; 548 ():113200.
Chicago/Turabian StyleStefanie Dohrn; Christian Luebbert; Kristin Lehmkemper; Samuel O. Kyeremateng; Matthias Degenhardt; Gabriele Sadowski. 2021. "Solvent mixtures in pharmaceutical development: Maximizing the API solubility and avoiding phase separation." Fluid Phase Equilibria 548, no. : 113200.
The formulation of active pharmaceutical ingredients (APIs) as pharmaceutical co-crystals (CCs) is a promising way to overcome the poor aqueous solubility and therewith poor bioavailability of many APIs. Identifying suitable coformers (CFs) that form CCs with the API is a major challenge during CC development. In this work, we developed a material-sparing and simple approach to identify whether a certain API/CF combination can form CCs. This approach is based on the solvent vapor sorption of API/CF combinations in a dynamic vapor-sorption apparatus. CC formation is detected based on the solvent vapor uptake behavior of an API/CF crystal mixture. This screening approach was applied for carbamazepine (CBZ)/nicotinamide and CBZ/acetylsalicylic acid systems using ethanol and methanol as the volatile solvents. CC formation was observed for both systems with both solvents used. Additionally, the process and success of CC formation by vapor sorption is explained by predicted phase diagrams using the Perturbed-Chain Statistical Associating Fluid Theory. The developed approach is beneficial over co-grinding and other batch crystallization approaches in that it can be performed with only a few milligrams of the API, low solvent consumption, and a solvent sorption versus time behavior for identifying CC formation.
Heiner Veith; Christian Luebbert; Naír Rodríguez-Hornedo; Gabriele Sadowski. Co-Crystal Screening by Vapor Sorption of Organic Solvents. Crystal Growth & Design 2021, 1 .
AMA StyleHeiner Veith, Christian Luebbert, Naír Rodríguez-Hornedo, Gabriele Sadowski. Co-Crystal Screening by Vapor Sorption of Organic Solvents. Crystal Growth & Design. 2021; ():1.
Chicago/Turabian StyleHeiner Veith; Christian Luebbert; Naír Rodríguez-Hornedo; Gabriele Sadowski. 2021. "Co-Crystal Screening by Vapor Sorption of Organic Solvents." Crystal Growth & Design , no. : 1.
Vapor pressures of the biologically and industrially relevant amines 2-phenylethan-1-amine, 2-amino-1-phenylethanol, α-(methylaminomethyl)benzyl alcohol, 1-phenylmethanamine, and N,N-diethylundecan-1-amine were measured via the transpiration method. Pure-component parameters for the thermodynamic model PC-SAFT were fitted to these vapor pressures and to liquid densities. The pure-component parameters were validated with measured liquid densities of binary mixtures dimethylsulfoxid + 4-(2-aminoethyl)phenol, dimethylsulfoxid + 2-amino-1-phenylethanol, dimethylsulfoxid + α-(methylaminomethyl)benzyl alcohol, and dimethylsulfoxid + 1-phenylmethanamine at 0.102 MPa and temperatures from 298.15 to 343.15 K at different amine mass fractions. Solid–liquid equilibria at 0.1 MPa were measured in binary mixtures of α-(methylaminomethyl)benzyl alcohol + water and 4-(2-aminoethyl)phenol + water at 298.15 and 308.15 K. Finally, the presence of liquid–liquid phase separation for these systems was qualitatively predicted using PC-SAFT based on the solid–liquid equilibria only and validated for the system α-(methylaminomethyl)benzyl alcohol + water by experiments at 293.15 and 323 K at 0.1 MPa.
Fabian Huxoll; Marcel Heyng; Irina V. Andreeva; Sergey P. Verevkin; Gabriele Sadowski. Thermodynamic Properties of Biogenic Amines and Their Solutions. Journal of Chemical & Engineering Data 2021, 66, 2822 -2831.
AMA StyleFabian Huxoll, Marcel Heyng, Irina V. Andreeva, Sergey P. Verevkin, Gabriele Sadowski. Thermodynamic Properties of Biogenic Amines and Their Solutions. Journal of Chemical & Engineering Data. 2021; 66 (7):2822-2831.
Chicago/Turabian StyleFabian Huxoll; Marcel Heyng; Irina V. Andreeva; Sergey P. Verevkin; Gabriele Sadowski. 2021. "Thermodynamic Properties of Biogenic Amines and Their Solutions." Journal of Chemical & Engineering Data 66, no. 7: 2822-2831.
Hydrogels are one of the emerging classes of materials in current research. Besides their numerous applications in the medical sector as a drug delivery system or in tissue replacement, they are also suitable as irrigation components or as immobilization matrices in catalysis. For optimal application of these compounds, knowledge of the swelling properties and the diffusion mechanisms occurring in the gels is mandatory. This study is focused on hydrogels synthesized by radical polymerization of imidazolium-based ionic liquids. Both the swelling and diffusion behavior of these hydrogels were investigated via gravimetric swelling as well as sorption experiments implemented in water, ethanol, n-heptane, and tetrahydrofuran. In water and ethanol, strong swelling was observed while the transport mechanism deviated from Fickian-type behavior. By varying the counterion and the chain length of the cation, their influences on the processes were observed. The calculation of the diffusion coefficients delivered values in the range of 10−10 to 10−12 m2 s−1. The gravimetric results were supported by apparent diffusion coefficients measured through diffusion-weighted magnetic resonance imaging. A visualization of the water diffusion front within the hydrogel should help to further elucidate the diffusion processes in the imidazolium-based hydrogels.
Ann Jastram; Tobias Lindner; Christian Luebbert; Gabriele Sadowski; Udo Kragl. Swelling and Diffusion in Polymerized Ionic Liquids-Based Hydrogels. Polymers 2021, 13, 1834 .
AMA StyleAnn Jastram, Tobias Lindner, Christian Luebbert, Gabriele Sadowski, Udo Kragl. Swelling and Diffusion in Polymerized Ionic Liquids-Based Hydrogels. Polymers. 2021; 13 (11):1834.
Chicago/Turabian StyleAnn Jastram; Tobias Lindner; Christian Luebbert; Gabriele Sadowski; Udo Kragl. 2021. "Swelling and Diffusion in Polymerized Ionic Liquids-Based Hydrogels." Polymers 13, no. 11: 1834.
The presence of water in the form of relative humidity (RH) may lead to deliquescence of crystalline components above a certain RH, the deliquescence RH (DRH). Knowing the DRH values is essential, e.g., for the agrochemical industry, food industry, and pharmaceutical industry to identify stability windows for their crystalline products. This work applies the Perturbed-Chain Statistical Associating Fluid Theory (PC-SAFT) to purely predict the DRH of single components (organic acids, sugars, artificial sweeteners, and amides) and multicomponent crystal mixtures thereof only based on aqueous solubility data of the pure components. The predicted DRH values very well agree with the experimental ones. In addition, the temperature influence on the DRH value could be successfully predicted with PC-SAFT. The DRH prediction also differentiates between formation of hydrates and anhydrates. PC-SAFT-predicted phase diagrams of hydrate-forming components illustrate the influence of additional components on the hydrate formation as a function of RH. The DRH prediction via PC-SAFT allows for the determining of the stability of crystals and crystal mixtures without the need for time-consuming experiments.
Heiner Veith; Christian Luebbert; Gabriele Sadowski. Predicting Deliquescence Relative Humidities of Crystals and Crystal Mixtures. Molecules 2021, 26, 3176 .
AMA StyleHeiner Veith, Christian Luebbert, Gabriele Sadowski. Predicting Deliquescence Relative Humidities of Crystals and Crystal Mixtures. Molecules. 2021; 26 (11):3176.
Chicago/Turabian StyleHeiner Veith; Christian Luebbert; Gabriele Sadowski. 2021. "Predicting Deliquescence Relative Humidities of Crystals and Crystal Mixtures." Molecules 26, no. 11: 3176.
Sour-gas absorption is the main unit operation used in refineries and petrochemical and natural gas processing plants for the effective reduction of climate-wrecking gases, mainly CO2 and H2S. Absorption is typically accomplished in an aqueous solvent mixture. The solvent mixture is vastly dependent on the application range; it might contain chemical solvents (amines), activators, and physical solvents. In this work, the vapor–liquid equilibria for absorption of the sour gases CO2 and H2S was investigated in systems containing the chemical solvent methyl diethanolamine (MDEA) and the physical solvents tetrahydrothiophene-1,1-dioxide (sulfolane) or the ionic liquid 1-butyl-3-methylimidazolium acetate. The solubilities of CO2 and H2S were predicted and validated using experimental literature data in a broad range of temperature (313–373 K), sour-gas loading (up to 2 moles gas per moles of MDEA), and pressure (up to 180 bar) at constant MDEA weight fraction (20.9 wt %) and sulfolane weight fraction (30.5 wt %). The equation-of-state electrolyte perturbed-chain statistical associating fluid theory (ePC-SAFT) was utilized in this work for the predictions combined with the Born term to physically correctly describe the Gibbs energy of solvation of ions in the aqueous mixture of chemical and physical solvents; this was introduced in a recent work [Bülow, M. Fluid Phase Equilib. 2021, 535, 112967]. Using this approach allowed reducing the total number of binary interaction parameters in these systems of maximum 11 species to a minimum; these parameters were fitted exclusively to data of binary mixtures. The ePC-SAFT predictions of the gas solubility were most accurate at low sour-gas loadings and high temperatures. This work provides a thermodynamic framework for the solvent selection for sour-gas absorption in a broad range of conditions. This enables a realistic decrease in experimental effort for solvent selection in sour-gas absorption.
Mark Bülow; Nevin Gerek Ince; Seiya Hirohama; Gabriele Sadowski; Christoph Held. Predicting Vapor–Liquid Equilibria for Sour-Gas Absorption in Aqueous Mixtures of Chemical and Physical Solvents or Ionic Liquids with ePC-SAFT. Industrial & Engineering Chemistry Research 2021, 60, 6327 -6336.
AMA StyleMark Bülow, Nevin Gerek Ince, Seiya Hirohama, Gabriele Sadowski, Christoph Held. Predicting Vapor–Liquid Equilibria for Sour-Gas Absorption in Aqueous Mixtures of Chemical and Physical Solvents or Ionic Liquids with ePC-SAFT. Industrial & Engineering Chemistry Research. 2021; 60 (17):6327-6336.
Chicago/Turabian StyleMark Bülow; Nevin Gerek Ince; Seiya Hirohama; Gabriele Sadowski; Christoph Held. 2021. "Predicting Vapor–Liquid Equilibria for Sour-Gas Absorption in Aqueous Mixtures of Chemical and Physical Solvents or Ionic Liquids with ePC-SAFT." Industrial & Engineering Chemistry Research 60, no. 17: 6327-6336.
Ramesh L. Gardas; David A. Kofke; Ronny Pini; Gabriele Sadowski; Cara E. Schwarz; J. Ilja Siepmann; Jiangtao Wu. Historical Perspective of the Journal of Chemical & Engineering Data’s Published Topics, 1956–2020. Journal of Chemical & Engineering Data 2021, 66, 1555 -1556.
AMA StyleRamesh L. Gardas, David A. Kofke, Ronny Pini, Gabriele Sadowski, Cara E. Schwarz, J. Ilja Siepmann, Jiangtao Wu. Historical Perspective of the Journal of Chemical & Engineering Data’s Published Topics, 1956–2020. Journal of Chemical & Engineering Data. 2021; 66 (4):1555-1556.
Chicago/Turabian StyleRamesh L. Gardas; David A. Kofke; Ronny Pini; Gabriele Sadowski; Cara E. Schwarz; J. Ilja Siepmann; Jiangtao Wu. 2021. "Historical Perspective of the Journal of Chemical & Engineering Data’s Published Topics, 1956–2020." Journal of Chemical & Engineering Data 66, no. 4: 1555-1556.
Knowledge of the stability of pharmaceutical formulations against relative humidity (RH) is essential if they are to become pharmaceutical products. The increasing interest in formulating active pharmaceutical ingredients as stable co-crystals (CCs) triggers the need for fast and reliable in-silico predictions of CC stability as a function of RH. CC storage at elevated RH can lead to deliquescence, which leads to CC dissolution and possible transformation to less soluble solid-state forms. In this work, the deliquescence RHs of the CCs succinic acid/nicotinamide, carbamazepine/nicotinamide, theophylline/citric acid, and urea/glutaric acid were predicted using the Perturbed-Chain Statistical Associating Fluid Theory (PC-SAFT). These deliquescence RH values together with predicted phase diagrams of CCs in water were used to determine critical storage conditions, that could lead to CC instability, that is, CC dissolution and precipitation of its components. The importance of CC phase purity on RH conditions for CC stability is demonstrated, where trace levels of a separate phase of active pharmaceutical ingredient or of coformer can significantly decrease the deliquescence RH. The use of additional excipients such as fructose or xylitol was predicted to decrease the deliquescence RH even further. All predictions were successfully validated by stability measurements at 58%, 76%, 86%, 93%, and 98% RH and 25 °C.
Heiner Veith; Maximilian Zaeh; Christian Luebbert; Naír Rodríguez-Hornedo; Gabriele Sadowski. Stability of Pharmaceutical Co-Crystals at Humid Conditions Can Be Predicted. Pharmaceutics 2021, 13, 433 .
AMA StyleHeiner Veith, Maximilian Zaeh, Christian Luebbert, Naír Rodríguez-Hornedo, Gabriele Sadowski. Stability of Pharmaceutical Co-Crystals at Humid Conditions Can Be Predicted. Pharmaceutics. 2021; 13 (3):433.
Chicago/Turabian StyleHeiner Veith; Maximilian Zaeh; Christian Luebbert; Naír Rodríguez-Hornedo; Gabriele Sadowski. 2021. "Stability of Pharmaceutical Co-Crystals at Humid Conditions Can Be Predicted." Pharmaceutics 13, no. 3: 433.
Amorphous solid dispersions (ASDs) are commonly manufactured using spray-drying processes. The product quality can be decisively influenced by the choice of process parameters. Following the quality-by-design approach, the identification of the spray-drying process design space is thus an integral task in drug product development. Aiming a solvent-free and homogeneous ASD, API crystallization and amorphous phase separation needs to be avoided during drying. This publication provides a predictive approach for determining spray-drying process conditions via considering thermodynamic driving forces for solvent drying as well as ASD-specific API/polymer/solvent interactions and glass transitions. The ternary API/polymer/solvent phase behavior was calculated using the Perturbed-Chain Statistical Associating Theory and combined with mass and energy balances to find appropriate spray-drying conditions. A process design space was identified for the ASDs of ritonavir and naproxen with either poly(vinylpyrrolidone) or poly(vinylpyrrolidone-co-vinylacetate) spray dried from the solvents acetone, dichloromethane, or ethanol.
Stefanie Dohrn; Pranay Rawal; Christian Luebbert; Kristin Lehmkemper; Samuel O. Kyeremateng; Matthias Degenhardt; Gabriele Sadowski. Predicting process design spaces for spray drying amorphous solid dispersions. International Journal of Pharmaceutics: X 2021, 3, 100072 .
AMA StyleStefanie Dohrn, Pranay Rawal, Christian Luebbert, Kristin Lehmkemper, Samuel O. Kyeremateng, Matthias Degenhardt, Gabriele Sadowski. Predicting process design spaces for spray drying amorphous solid dispersions. International Journal of Pharmaceutics: X. 2021; 3 ():100072.
Chicago/Turabian StyleStefanie Dohrn; Pranay Rawal; Christian Luebbert; Kristin Lehmkemper; Samuel O. Kyeremateng; Matthias Degenhardt; Gabriele Sadowski. 2021. "Predicting process design spaces for spray drying amorphous solid dispersions." International Journal of Pharmaceutics: X 3, no. : 100072.
In this work we investigated the solubilities of 10 active pharmaceutical ingredients (APIs), namely, fenofibrate, ibuprofen, cinnarizine, carbamazepine, indomethacin, naproxen, griseofulvin, glibenclamide, felodipine, and praziquantel in the pharmaceutically relevant excipients tricaprylin, Lauroglycol FCC, Capryol 90, Kolliphor TPGS, ethanol, and monolaurin. API solubilities were either determined gravimetrically, with high-performance liquid chromatography, or with differential scanning calorimetry. Mutual solubilities in the three possible mixtures out of Kolliphor TPGS, tricaprylin, and carbitol as well as the vapor sorption of ethanol in tricaprylin were determined experimentally. The Perturbed-Chain Statistical Associating Fluid Theory (PC-SAFT) pure-component parameters for seven APIs were determined via fitting to vapor pressures and liquid densities or to solubilities in organic solvents. In total, 80 binary interaction parameters were fitted to the investigated binary mixtures. They can be used in the future to improve the accuracy of lipid-based drug delivery systems in-silico screenings with PC-SAFT.
Joscha Brinkmann; Lara Exner; Sergey P. Verevkin; Christian Luebbert; Gabriele Sadowski. PC-SAFT Modeling of Phase Equilibria Relevant for Lipid-Based Drug Delivery Systems. Journal of Chemical & Engineering Data 2021, 66, 1280 -1289.
AMA StyleJoscha Brinkmann, Lara Exner, Sergey P. Verevkin, Christian Luebbert, Gabriele Sadowski. PC-SAFT Modeling of Phase Equilibria Relevant for Lipid-Based Drug Delivery Systems. Journal of Chemical & Engineering Data. 2021; 66 (3):1280-1289.
Chicago/Turabian StyleJoscha Brinkmann; Lara Exner; Sergey P. Verevkin; Christian Luebbert; Gabriele Sadowski. 2021. "PC-SAFT Modeling of Phase Equilibria Relevant for Lipid-Based Drug Delivery Systems." Journal of Chemical & Engineering Data 66, no. 3: 1280-1289.
J. Ilja Siepmann; Ramesh L. Gardas; David A. Kofke; Ronny Pini; Gabriele Sadowski; Cara E. Schwarz; Jiangtao Wu. Journal of Chemical & Engineering Data: Why Change the Cover Page? Journal of Chemical & Engineering Data 2021, 66, 859 -860.
AMA StyleJ. Ilja Siepmann, Ramesh L. Gardas, David A. Kofke, Ronny Pini, Gabriele Sadowski, Cara E. Schwarz, Jiangtao Wu. Journal of Chemical & Engineering Data: Why Change the Cover Page? Journal of Chemical & Engineering Data. 2021; 66 (2):859-860.
Chicago/Turabian StyleJ. Ilja Siepmann; Ramesh L. Gardas; David A. Kofke; Ronny Pini; Gabriele Sadowski; Cara E. Schwarz; Jiangtao Wu. 2021. "Journal of Chemical & Engineering Data: Why Change the Cover Page?" Journal of Chemical & Engineering Data 66, no. 2: 859-860.
The dissolution behavior of novel active pharmaceutical ingredients (API) is a crucial parameter in drug formulation since it frequently affects the drug release. Generally, a distinction is made between surface-reaction- and diffusion-controlled drug release. Therefore, dissolution studies such as the intrinsic dissolution test defined in the pharmacopeia have been performed for many years. In order to overcome the disadvantages of the common intrinsic dissolution test, a new experimental setup was developed within this study. Specifically, a flow channel was designed and tested for measuring the mass transfer from a flat, solid surface dissolving into a fluid flowing over the surface with well-defined flow conditions. A mathematical model was developed that distinguishes between surface-reaction- and diffusion-limited drug release based on experimental data. Three different drugs—benzocaine, theophylline and griseofulvin—were used to investigate the mass flux during dissolution due to surface reaction, diffusion and convection kinetics. This new technique shows potential to be a valuable tool for the identification of formulation strategies.
Dominik Sleziona; Amelie Mattusch; Gerhard Schaldach; David Ely; Gabriele Sadowski; Markus Thommes. Determination of Inherent Dissolution Performance of Drug Substances. Pharmaceutics 2021, 13, 146 .
AMA StyleDominik Sleziona, Amelie Mattusch, Gerhard Schaldach, David Ely, Gabriele Sadowski, Markus Thommes. Determination of Inherent Dissolution Performance of Drug Substances. Pharmaceutics. 2021; 13 (2):146.
Chicago/Turabian StyleDominik Sleziona; Amelie Mattusch; Gerhard Schaldach; David Ely; Gabriele Sadowski; Markus Thommes. 2021. "Determination of Inherent Dissolution Performance of Drug Substances." Pharmaceutics 13, no. 2: 146.
Partitioning tests in water are early-stage standard experiments during the development of pharmaceutical formulations, e.g. of lipid-based drug delivery system (LBDDS). The partitioning behavior of the active pharmaceutical ingredient (API) between the fatty phase and the aqueous phase is a key property, which is supposed to be determined by those tests. In this work, we investigated the API partitioning between LBDDS and water by in-silico predictions applying the Perturbed-Chain Statistical Associating Fluid Theory (PC-SAFT) and validated these predictions experimentally. The API partitioning was investigated for LBDDS comprising up to four components (cinnarizine or ibuprofen with tricaprylin, caprylic acid, and ethanol). The influence of LBDDS/water mixing ratios from 1/1 up to 1/200 (w/w) as well as the influence of excipients on the API partitioning was studied. Moreover, possible API crystallization upon mixing the LBDDS with water was predicted. This work showed that PC-SAFT is a strong tool for predicting the API partitioning behavior during in-vitro tests. Thus, it allows rapidly assessing whether or not a specific LBDDS might be a promising candidate for further in-vitro tests and identifying the API load up to which API crystallization can be avoided.
Joscha Brinkmann; Isabel Becker; Peter Kroll; Christian Luebbert; Gabriele Sadowski. Predicting the API partitioning between lipid-based drug delivery systems and water. International Journal of Pharmaceutics 2021, 595, 120266 .
AMA StyleJoscha Brinkmann, Isabel Becker, Peter Kroll, Christian Luebbert, Gabriele Sadowski. Predicting the API partitioning between lipid-based drug delivery systems and water. International Journal of Pharmaceutics. 2021; 595 ():120266.
Chicago/Turabian StyleJoscha Brinkmann; Isabel Becker; Peter Kroll; Christian Luebbert; Gabriele Sadowski. 2021. "Predicting the API partitioning between lipid-based drug delivery systems and water." International Journal of Pharmaceutics 595, no. : 120266.
Deep eutectic solvents have appeared as potential solvents for improving the extraction of polyphenols from vegetable or fruit matrixes. Since gallic acid is abundant in these sources, it is considered as a typical standard for quantifying their total polyphenol content after extraction with solvents. However, there are no extensive studies on the solubility behavior of gallic acid in different solvents or deep eutectic solvents. Thus, in this work, the solubility of gallic acid is measured in pure water; aqueous solutions of different hydrogen bond donors such as ethylene glycol, levulinic acid, and glycerol; and aqueous mixtures of deep eutectic solvents using choline chloride as the hydrogen bond acceptor and ethylene glycol, levulinic acid, and glycerol as the hydrogen bond donors. All of the measurements were performed at 293.15, 303.15, and 313.15 K and at 101.3 kPa and were validated by comparing the solubility of gallic acid in water from the literature. Results suggest that a 50 wt % aqueous solution of deep eutectic solvent based on ethylene glycol or glycerol improves the gallic acid solubility compared with a 50 wt % aqueous solution of its corresponding hydrogen bond donor. The deep eutectic solvent containing levulinic acid acts as the best aqueous mixture for gallic acid dissolution. Nondissolved gallic acid was measured after equilibrium using powder X-ray diffraction, showing that its structure does not change upon mixing with all of the liquid mixtures. All of the solid–liquid equilibrium results were accurately modeled with perturbed-chain statistical associating fluid theory (PC-SAFT).
Bruno Sepúlveda-Orellana; Nicolás F. Gajardo-Parra; Hoang T. Do; José R. Pérez-Correa; Christoph Held; Gabriele Sadowski; Roberto I. Canales. Measurement and PC-SAFT Modeling of the Solubility of Gallic Acid in Aqueous Mixtures of Deep Eutectic Solvents. Journal of Chemical & Engineering Data 2021, 66, 958 -967.
AMA StyleBruno Sepúlveda-Orellana, Nicolás F. Gajardo-Parra, Hoang T. Do, José R. Pérez-Correa, Christoph Held, Gabriele Sadowski, Roberto I. Canales. Measurement and PC-SAFT Modeling of the Solubility of Gallic Acid in Aqueous Mixtures of Deep Eutectic Solvents. Journal of Chemical & Engineering Data. 2021; 66 (2):958-967.
Chicago/Turabian StyleBruno Sepúlveda-Orellana; Nicolás F. Gajardo-Parra; Hoang T. Do; José R. Pérez-Correa; Christoph Held; Gabriele Sadowski; Roberto I. Canales. 2021. "Measurement and PC-SAFT Modeling of the Solubility of Gallic Acid in Aqueous Mixtures of Deep Eutectic Solvents." Journal of Chemical & Engineering Data 66, no. 2: 958-967.
J. Ilja Siepmann; Ramesh L. Gardas; David A. Kofke; Ronny Pini; Gabriele Sadowski; Cara E. Schwarz; Jiangtao Wu. Journal of Chemical & Engineering Data: An Update from the Editorial Team. Journal of Chemical & Engineering Data 2021, 66, 1 -2.
AMA StyleJ. Ilja Siepmann, Ramesh L. Gardas, David A. Kofke, Ronny Pini, Gabriele Sadowski, Cara E. Schwarz, Jiangtao Wu. Journal of Chemical & Engineering Data: An Update from the Editorial Team. Journal of Chemical & Engineering Data. 2021; 66 (1):1-2.
Chicago/Turabian StyleJ. Ilja Siepmann; Ramesh L. Gardas; David A. Kofke; Ronny Pini; Gabriele Sadowski; Cara E. Schwarz; Jiangtao Wu. 2021. "Journal of Chemical & Engineering Data: An Update from the Editorial Team." Journal of Chemical & Engineering Data 66, no. 1: 1-2.
An information theory-based methodology has been applied to the multiproperty modeling of solution properties. Under this framework, a practical application on a set of binary solutions formed by dimethyl carbonate and six even saturated hydrocarbons (from C6 to C16) is carried out. A dense experimental database is generated composed of volumetric and energetic properties (from mixing processes), and phase equilibria, in order to disambiguate some discrepancies showed by the literature data, mainly for the binary with dodecane. The experimental information is modeled with a semiempirical equation for gE, and with the PCP-SAFT equation of state, which presents a solid theoretical basis. The optimal parameterizations are sought using the precision–complexity binomial whose aim is to increase the validity range of the set of parameters obtained. The Akaike Information Criterion is used to search the best parameterizations, that is, the appropriate number of parameters (complexity) and their best values (precision). With regard to the suitability of the precision–complexity methodology on the models tested, the following is concluded: with PCP-SAFT, precise and reliable estimates are obtained; for the gE model, the proposed approach is essential to control the number of free parameters and to preserve the stable numerical behavior in a wide range of conditions.
Adriel Sosa; Juan Ortega; Luís Fernández; Niklas Haarmann; Gabriele Sadowski. Methodology Based on the Theory of Information to Describe the Representation Ability of the DMC + Alkane Behavior. Industrial & Engineering Chemistry Research 2021, 60, 1036 -1054.
AMA StyleAdriel Sosa, Juan Ortega, Luís Fernández, Niklas Haarmann, Gabriele Sadowski. Methodology Based on the Theory of Information to Describe the Representation Ability of the DMC + Alkane Behavior. Industrial & Engineering Chemistry Research. 2021; 60 (2):1036-1054.
Chicago/Turabian StyleAdriel Sosa; Juan Ortega; Luís Fernández; Niklas Haarmann; Gabriele Sadowski. 2021. "Methodology Based on the Theory of Information to Describe the Representation Ability of the DMC + Alkane Behavior." Industrial & Engineering Chemistry Research 60, no. 2: 1036-1054.
Solvents have an enormous impact on yield and turnover of chemical reactions in complex media. There is, however, a lack of consistent model-based tools to a priori identify the appropriate solvent for homogeneously catalyzed reactions. Here, a thermodynamically consistent approach for a reductive amination reaction is presented. It combines solvent screening using a thermodynamic-activity model and quantum chemical calculations. The optimization of activity coefficient-based predicted kinetics gives a suitable list of candidate solvents. The results were confirmed by batch experiments in selected solvents. This approach allows reducing time and lab resources for solvent selection to a minimum.
Fabian Huxoll; Froze Jameel; Jonas Bianga; Thomas Seidensticker; Matthias Stein; Gabriele Sadowski; Dieter Vogt. Solvent Selection in Homogeneous Catalysis—Optimization of Kinetics and Reaction Performance. ACS Catalysis 2020, 11, 590 -594.
AMA StyleFabian Huxoll, Froze Jameel, Jonas Bianga, Thomas Seidensticker, Matthias Stein, Gabriele Sadowski, Dieter Vogt. Solvent Selection in Homogeneous Catalysis—Optimization of Kinetics and Reaction Performance. ACS Catalysis. 2020; 11 (2):590-594.
Chicago/Turabian StyleFabian Huxoll; Froze Jameel; Jonas Bianga; Thomas Seidensticker; Matthias Stein; Gabriele Sadowski; Dieter Vogt. 2020. "Solvent Selection in Homogeneous Catalysis—Optimization of Kinetics and Reaction Performance." ACS Catalysis 11, no. 2: 590-594.
Novel polymeric carriers for amorphous solid dispersions (ASDs) are highly demanded in pharmaceutical industry to improve the bioavailability of poorly-soluble drug candidates. Besides established polymer candidates, hydroxypropyl celluloses (HPC) comes more and more into the focus of ASD production since they have the availability to stabilize drug molecules in aqueous media against crystallization. The thermodynamic long-term stability of HPC ASDs with itraconazole and fenofibrate was predicted in this work with PC-SAFT and compared to three-months enduring long-term stability studies. The glass-transition temperature is a crucial attribute of a polymer, but in case of HPC hardly detectable by differential scanning calorimetry. By investigating the glass transition of HPC blends with a miscible polymer, we were for the first time able to estimate the HPC glass transition. Although both, fenofibrate and itraconazole reveal a very low crystalline solubility in HPC regardless of the HPC molecular weight, we observed that low-molecular weight HPC grades such as HPC-UL prevent fenofibrate crystallization for a longer period than the higher molecular weight HPC grades. As predicted, the ASDs with higher drug load underwent amorphous phase separation according to the differential scanning calorimetry thermograms. This work thus showed that it is possible to predict critical drug loads above which amorphous phase separation and/or crystallization occurs in HPC ASDs.
Christian Luebbert; Edmont Stoyanov; Gabriele Sadowski. Phase behavior of ASDs based on hydroxypropyl cellulose. International Journal of Pharmaceutics: X 2020, 3, 100070 .
AMA StyleChristian Luebbert, Edmont Stoyanov, Gabriele Sadowski. Phase behavior of ASDs based on hydroxypropyl cellulose. International Journal of Pharmaceutics: X. 2020; 3 ():100070.
Chicago/Turabian StyleChristian Luebbert; Edmont Stoyanov; Gabriele Sadowski. 2020. "Phase behavior of ASDs based on hydroxypropyl cellulose." International Journal of Pharmaceutics: X 3, no. : 100070.
Gabriele Sadowski. Special Issue Celebrating 30 Years of SAFT. Journal of Chemical & Engineering Data 2020, 65, 5627 -5627.
AMA StyleGabriele Sadowski. Special Issue Celebrating 30 Years of SAFT. Journal of Chemical & Engineering Data. 2020; 65 (12):5627-5627.
Chicago/Turabian StyleGabriele Sadowski. 2020. "Special Issue Celebrating 30 Years of SAFT." Journal of Chemical & Engineering Data 65, no. 12: 5627-5627.
Amorphous solid dispersions (ASDs) are often metastable against crystallization of the active pharmaceutical ingredient (API) and thus might undergo unwanted changes during storage. The crystallization tendency of ASDs is influenced by the API crystallization driving force (CDF) and the mobility of the molecules in the ASD. Low molecular weight-excipients are known to stabilize amorphous APIs in so-called co-amorphous formulations. Due to their success in stabilizing co-amorphous APIs, low-molecular weight excipients might also enhance the stability of polymeric ASDs. In this work, we investigated the potential of combined low-molecular weight excipient/polymer formulations with in-silico tools and validated the predictions with long-term stability tests of the most promising excipient/polymer combinations. The considered critical quality attributes for the ASDs were the occurrence of amorphous phase separation, API CDF, and molecular mobility in the ASD. As an example, carbamazepine/polyvinylpyrrolidone ASDs were investigated combined with the excipients fructose, lactose, sucrose, trehalose, saccharin, tryptophan, and urea. Although all excipients had a negative impact on the ASD stability, saccharin still turned out to be the most promising one. Long-term stability studies with ASDs containing either saccharin or tryptophan verified -in agreement to the predictions- that API crystallization occurred faster than in the reference ASDs without additional excipient. This work showed that the addition of crystalline excipients to polymeric ASDs might not only offer opportunities but might also bear risks for the long-term stability of the ASD, even though the crystalline excipient stabilizes the polymer-free API. Consequently, excipients should be evaluated based on the thermodynamic phase behavior of the individual mixture of API/polymer/excipient, rather than based on pure-component properties of the excipient only. In-silico predictions proposed in this work remarkably decrease the number of screening tests for identifying suitable formulation excipients.
Heiner Veith; Felix Wiechert; Christian Luebbert; Gabriele Sadowski. Combining crystalline and polymeric excipients in API solid dispersions – Opportunity or risk? European Journal of Pharmaceutics and Biopharmaceutics 2020, 158, 323 -335.
AMA StyleHeiner Veith, Felix Wiechert, Christian Luebbert, Gabriele Sadowski. Combining crystalline and polymeric excipients in API solid dispersions – Opportunity or risk? European Journal of Pharmaceutics and Biopharmaceutics. 2020; 158 ():323-335.
Chicago/Turabian StyleHeiner Veith; Felix Wiechert; Christian Luebbert; Gabriele Sadowski. 2020. "Combining crystalline and polymeric excipients in API solid dispersions – Opportunity or risk?" European Journal of Pharmaceutics and Biopharmaceutics 158, no. : 323-335.