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Heiner Veith is PhD candidate in the Department of Biochemical and Chemical Engineering at TU Dortmund University. He has been a researcher in the Laboratory of Thermodynamics at TU Dortmund University since 2018. His current research is concerned with the thermodynamic stability of polymorphs, hydrates, solvates, and co-crystals of pharmaceuticals.
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.
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.
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 (ASD) are state-of-the art enabling formulations for poorly water-soluble active pharmaceutical ingredients (APIs). Depending on the relative humidity (RH), temperature, and API content, ASDs are often metastable against crystallization of the API or even against the formation of API hydrates in the ASD. Knowing the conditions at which API crystals or API hydrate formation may occur in ASDs therefore is an important prerequisite for developing a suitable formulation strategy for APIs. ASDs containing hydrate-forming APIs (carbamazepine/polyvinylpyrrolidone, carbamazepine/hydroxypropylmethylcellulose acetate succinate, and theophylline/polyvinylpyrrolidone) were investigated in this work. The influence of polymer type, RH, API content, and water sorption on the ASD stability was determined via phase diagrams predicted using the Perturbed-Chain Statistical Associating Fluid Theory (PC-SAFT). These predictions were successfully validated by long-term stability tests at 295 K and 0%, 58%, 76%, 86%, and 93% RH. Hydrate crystals are formed above their critical RH. Thus, ASDs with carbamazepine (critical RH 65% at 295 K) as well as theophylline (critical RH 58% RH) showed hydrate crystals at 76%, 86% and 93% RH, no matter which polymer was used for preparing the ASD.
Heiner Veith; Erol Turan; Christian Luebbert; Gabriele Sadowski. Hydrate formation in polymer-based pharmaceutical formulations. Fluid Phase Equilibria 2020, 521, 112677 .
AMA StyleHeiner Veith, Erol Turan, Christian Luebbert, Gabriele Sadowski. Hydrate formation in polymer-based pharmaceutical formulations. Fluid Phase Equilibria. 2020; 521 ():112677.
Chicago/Turabian StyleHeiner Veith; Erol Turan; Christian Luebbert; Gabriele Sadowski. 2020. "Hydrate formation in polymer-based pharmaceutical formulations." Fluid Phase Equilibria 521, no. : 112677.
The formation of solvates, hydrates, or different polymorphs significantly alters the physico-chemical properties of a target component (TC) (e.g. active pharmaceutical or agrochemical active ingredient), such as solubility and dissolution behavior. Thus, it is very important to know under which conditions a certain solvate, hydrate, or polymorph is formed. This information can be obtained from phase diagrams which are usually based on solubility measurements. Possible pitfalls in measuring the solubility of TC hydrates or solvates in solvents and solvent mixtures are discussed and strategies for obtaining reliable solubility data are proposed. To substantiate the proposed solubility-measurement strategies, a thermodynamic approach based on the Perturbed-Chain Statistical Associating Fluid Theory (PC-SAFT) for modeling solvate/hydrate solubilities was developed. This approach allows identifying stability regions of solvates/hydrates and predicting solubilities of solvates/hydrates or of polymorphs in pure solvents and solvent mixtures. It was successfully verified for modeling the solubility of the indomethacin-methanol solvate in methanol and of the carbamazepine dihydrate in water. Furthermore, the solubility of carbamazepine dihydrate and theophylline monohydrate in water/ethanol mixtures was predicted in excellent agreement with experimental data.
Heiner Veith; Christian Luebbert; Gabriele Sadowski. Correctly Measuring and Predicting Solubilities of Solvates, Hydrates, and Polymorphs. Crystal Growth & Design 2020, 20, 723 -735.
AMA StyleHeiner Veith, Christian Luebbert, Gabriele Sadowski. Correctly Measuring and Predicting Solubilities of Solvates, Hydrates, and Polymorphs. Crystal Growth & Design. 2020; 20 (2):723-735.
Chicago/Turabian StyleHeiner Veith; Christian Luebbert; Gabriele Sadowski. 2020. "Correctly Measuring and Predicting Solubilities of Solvates, Hydrates, and Polymorphs." Crystal Growth & Design 20, no. 2: 723-735.
Co-crystallization is a promising strategy to enhance the water solubility and bioavailability of active pharmaceutical ingredients (APIs). Once possible co-formers have been identified, suitable process conditions for an effective generation of pure co-crystals have to be found. In this work, two screening approaches have been developed to find the best-suited solvent and optimum process conditions for co-crystal formation: a shortcut approach based on mass balances and a second one which additionally accounts for thermodynamic non-idealities between the API, the co-former, and the solvent via the Perturbed-Chain Statistical Associating Fluid Theory (PC-SAFT). The enhanced efficiency of the two approaches compared to conventional ones is demonstrated for the two co-crystal-forming systems carbamazepine/ acetylsalicylic acid and carbamazepine/ salicylic acid. Appropriate conditions for co-crystal formation were identified in the solvents ethanol, ethyl acetate, acetonitrile, and methanol using the novel screening approaches. Phase diagrams were predicted using PC-SAFT and validated by experiments. It will be shown, that the co-crystal screening approach based on thermodynamic predictions yields an appropriate preselection of suitable solvents and thus can be used to determine best-performing solvents for co-crystal production with minimal experimental effort.
Heiner Veith; Miko Schleinitz; Carsten Schauerte; Gabriele Sadowski. Thermodynamic Approach for Co-crystal Screening. Crystal Growth & Design 2019, 19, 3253 -3264.
AMA StyleHeiner Veith, Miko Schleinitz, Carsten Schauerte, Gabriele Sadowski. Thermodynamic Approach for Co-crystal Screening. Crystal Growth & Design. 2019; 19 (6):3253-3264.
Chicago/Turabian StyleHeiner Veith; Miko Schleinitz; Carsten Schauerte; Gabriele Sadowski. 2019. "Thermodynamic Approach for Co-crystal Screening." Crystal Growth & Design 19, no. 6: 3253-3264.
Process synthesis and intensification are powerful tools for the development of cost- and energy-efficient chemical processes. However, even though their combination maximises the potential for improvements, they are mostly applied separately. The current article presents the extension of a phenomena-based process synthesis method by an aditional building block for reactor network synthesis and reactive separations. The method facilitates the automatic generation of thermodynamically feasible phenomena-based flowsheet variants by means of superstructure optimisation, which are subsequently translated into equipment-based flowsheets taking into account classical as well as intensified equipment. By composing a flowsheet from mass and energy transfer phenomena instead of pre-defined unit operations, counter-intuitive solutions and significant improvements can be achieved. In the current contribution, the capabilities of the method are demonstrated using the transesterification of propylene carbonate with methanol as a case study. The resulting optimal flowsheet represents a combination of integrated and hybrid separation steps for overcoming the intrinsic limitations of this system. The obtained result presents significant cost saving potential compared to those flowsheet variants previously generated by an alternative process synthesis method.
Hanns Kuhlmann; Heiner Veith; Marcel Moeller; Kieu-Phi Nguyen; Andrzej Gorak; Mirko Skiborowski. Optimization-Based Approach to Process Synthesis for Process Intensification: Synthesis of Reaction-Separation Processes. Industrial & Engineering Chemistry Research 2017, 57, 3639 -3655.
AMA StyleHanns Kuhlmann, Heiner Veith, Marcel Moeller, Kieu-Phi Nguyen, Andrzej Gorak, Mirko Skiborowski. Optimization-Based Approach to Process Synthesis for Process Intensification: Synthesis of Reaction-Separation Processes. Industrial & Engineering Chemistry Research. 2017; 57 (10):3639-3655.
Chicago/Turabian StyleHanns Kuhlmann; Heiner Veith; Marcel Moeller; Kieu-Phi Nguyen; Andrzej Gorak; Mirko Skiborowski. 2017. "Optimization-Based Approach to Process Synthesis for Process Intensification: Synthesis of Reaction-Separation Processes." Industrial & Engineering Chemistry Research 57, no. 10: 3639-3655.
The distribution coefficients and selectivities required for extraction purposes were predicted with a thermodynamic equation of state for the ternary system formic acid/water/extraction solvent. These predictions were validated with experimental data from the literature and experimental data from the oxidation of biomass to formic acid process measured in this work. Extraction solvents discussed in this work are 1-butanol, 1-pentanol, 1-hexanol, 1-heptanol, 1-octanol, 1-decanol, ethyl n-butyl ether, diisopropyl ether, di-n-butyl ether, benzyl formate, and heptyl formate. The considered temperature ranged from 273 to 363 K under atmospheric pressure. Perturbed-chain statistical associating fluid theory (PC-SAFT) was used for prediction purposes applying an approach as simple as possible and as complex as necessary to achieve trustworthy data for selecting the best extraction solvent. Using PC-SAFT allowed identifying 1-hexanol as the most promising solvent out of the 11 extraction agents. The predicted data were in good agreement with the experimental distribution coefficients and the selectivities, which are very sensitive to experimental uncertainties.
Heiner Veith; Matthias Voges; Christoph Held; Jakob Albert. Measuring and Predicting the Extraction Behavior of Biogenic Formic Acid in Biphasic Aqueous/Organic Reaction Mixtures. ACS Omega 2017, 2, 8982 -8989.
AMA StyleHeiner Veith, Matthias Voges, Christoph Held, Jakob Albert. Measuring and Predicting the Extraction Behavior of Biogenic Formic Acid in Biphasic Aqueous/Organic Reaction Mixtures. ACS Omega. 2017; 2 (12):8982-8989.
Chicago/Turabian StyleHeiner Veith; Matthias Voges; Christoph Held; Jakob Albert. 2017. "Measuring and Predicting the Extraction Behavior of Biogenic Formic Acid in Biphasic Aqueous/Organic Reaction Mixtures." ACS Omega 2, no. 12: 8982-8989.