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Pharmaceutical Formulations

Reaction Equilibria and Reaction Kinetics


Current Research Projects:


Solvate and Hydrate Formation of Pharamaceuticals


Many Active Pharmaceutical Ingredients (API) might be present in different solid states (different polymorphs, hydrates, solvates, salts, or cocrystals). All those solid forms result in completely different physico-chemical properties and therefore need to be characterized in detail during the development of a pharmaceutical formulation. Commonly, the different solid forms of an API are determined via time-consuming and expensive screening approaches.


Thermodynamic and Kinetic Stability of Amorphous Solid Dispersions (ASDs)


One of the biggest challenges in pharmaceutical development is the poor solubility of most active pharmaceutical ingredients (APIs) in the fluids of the gastrointestinal tract. A promising strategy to overcome this solubility limit is dissolving the API in a polymer matrix, generating a so-called amorphous solid dispersion (ASD) formulation. In this project, the influence of the preparation method and different storage conditions on the long-term stability of ASDs against API crystallization is investigated.


Solvent-induced phase separation in pharmaceutical formulations


Active Pharmaceutical ingredients (APIs) with a poor aqueous solubility present a major challenge in the pharmaceutical industry because of the resulting poor bioavailability. An established strategy to overcome this limitation is incorporating the API in a polymeric matrix, generating a so-called amorphous solid dispersion (ASD). An ASD might be produced via solvent-based processes, e.g. spray drying. The organic solvent used during the preparation might influence decisively the product quality of ASD formulations.


Increasing Protein Solubility for High-Concentration Protein Formulations using Advanced Additives


The application of monoclonal antibodies and proteins is an emerging field in biotechnology due to their high specificity with antigens [1]. However, most of the proteins have a poor solubility in water and therefore their application is mostly limited to intravenous administration. In the course of this work, suitable additives shall be identified that increase the protein concentration up to 150 to 200 mg mL-1 to enable subcutaneous administration of these formulations with higher patient compliance.


Supersaturation behavior of amorphous formulations of active pharmaceutical ingredients (API)


The low aqueous solubility of crystalline APIs often leads to their slow dissolution and insufficient oral bioavailability. Amorphous formulations, where the amorphous API is incorporated into hydrophilic polymeric excipients, have been demonstrated to yield concentrations above equilibrium solubility of the crystalline API, thus enhancing intestinal absorption. To prevent API recrystallization in the intestinal tract upon dissolution of the amorphous form, it is essential to develop theoretical models to understand and even predict the dissolution/recrystallization phenomena at API supersaturation.


Amorphous-amorphous phase separation in polymeric API systems


More than 90% of newly-developed active pharmaceutical ingredients (API) are currently rejected during drug development due to their low bioavailability. One promising approach to overcome this limitation is the formulation of an API in its amorphous state. This thermodynamically instable state is effectively stabilized by incorporating the API in a polymeric matrix. The project focuses on the experimental investigation and thermodynamic modeling of the amorphous-amorphous phase separation in API/polymer systems.


Dissolution of formulated poorly water-soluble pharmaceuticals


The development of potentially efficacious pharmaceuticals is hindered by their poor aqueous solubilities which result in a poor bioavailability. Our research focus on the dissolution mechanism and rate of formulated poorly water-soluble pharmaceuticals in solutions with experiments and theoretical modeling. It is expected that the research could provide useful knowledge for the formulation strategy development of poorly water-soluble amorphous pharmaceuticals.


Co-solute and co-solvent influence on the reaction equilibria of enzymatic catalyzed reactions


In literature co-solvent and co-solute effects on thermodynamic reaction equilibria of only a few enzymatic reactions were studied so far. In most cases the reaction media is pure water or a low concentrated buffered solution. This simplification of the highly non-ideal solutions present in cells leads to a lack of information and understanding of these complex systems. As a first approach to understand these complex interactions, this work is focused on the prediction of co-solvents and co-solute effects on the reaction equilibria of enzyme-catalyzed reactions.


Completed Research Projects in the group:


Phase behavior of pharmaceutical formulations


Excipient enhanced solubility of pharmaceuticals


Solvent effects on reaction equilibria and reaction kinetics


Thermodynamics of enzyme-catalyzed reactions in organic media


Predicting phase behavior of aqueous-protein solutions


Solubility behavior of pharmaceutical cocrystals


Crystallization of pharmaceutical proteins – Predicting protein solubility


Prediction of the extraction behavior of pharmaceuticals


Investigation of dissolution rates of poorly soluble pharmaceuticals


Solubility and bioavailability of pharmaceutical agents


Liquid-liquid equilibria of systems containing terpenes and amines


Measurement and modeling of the solubility and diffusivity of solvents in shape memory polymers


Measuring and modeling high-pressure gas solubility in temperature modulated solvent systems


Thermodynamic modelling of hydrogels


Measurement and modeling of oxygen diffusion in an intelligent indicator/polymer matrix


Layer melt crystallization of long-chain aldehydes from hydroformylation processes




Foto von Prof. Dr. Gabriele Sadowski

Prof. Dr. Gabriele Sadowski


TU Dortmund
Fakultät Bio- und Chemieingenieurwesen
Emil-Figge-Str. 70
44227 Dortmund

Raum G2-519a