Solid State Pharmaceutics
The primary mission of the group is to develop pharmaceutical approaches to increase the quality and performance of solid dosage forms, based on investigating the underlying principles behind molecular mobility of drugs and excipients, their interaction with each other, and their connection to pharmaceutical performance.
The research in the Solid State Pharmaceutics group is naturally centred on the solid state of pharmaceutical preparations. In the area of small molecular drug molecules, an increasing portion of drugs shows low aqueous solubility. This low solubility often severely reduces the bioavailability of the drug and may lead to pharmacologically effective molecules being abandoned. The transformation of a drug from the crystalline state to a high-energy amorphous form generally leads to an increase in solubility. However, as the amorphous form is inherently unstable, technological approaches are necessary to stabilise amorphous drugs. In our group, these include stabilizing excipients such as polymeric carriers, small molecules in co-amorphous formulations as well as mesoporous silica. Furthermore, we have developed approaches that allow an in situ amorphization of the crystalline drug in the final dosage form, e.g. by microwaves, which potentially allows to circumvent the long-term stabilization of the amorphous drug.
“The most active form of a drug frequently is an unstable variant and our research thus focusses on stabilizing the unstable” says group leader Dr. Holger Grohganz. With regard to larger molecules such as proteins, freeze-drying is widely used in production, although the interactions between various excipients and proteins are not fully understood. Our aim is to obtain a deeper understanding of the influence of various composition and process parameters on the solid state form of both the excipient and the macromolecule.
Over the recent years, we were world leading in acquiring in-depth knowledge on the formation likelihood, mechanism and stability of co-amorphous systems. Starting from the idea of using amino acids as co-formers, we have investigated which co-formers are most likely to form a stable co-amorphous system and the reasons behind this behaviour. In addition, we have performed investigations on neat amorphous molecules with regard to their likelihood to become and remain amorphous. A key discovery here is that local molecular mobility plays a bigger role as assumed so far. We have also developed advanced analytical techniques for thermal and surface characterization of amorphous forms. In addition, we aim to obtain a deeper understanding of the interactions between drug and excipient in freeze-dried pharmaceuticals.
Glass-Transition Temperature of the β-Relaxation as the Major Predictive Parameter for Recrystallization of Neat Amorphous Drugs. Eric Ofosu Kissi, Holger Grohganz, Korbinian Löbmann, Michael T. Ruggiero, J. Axel Zeitler, and Thomas Rades. The Journal of Physical Chemistry B 2018 122 (10), 2803-2808. DOI: 10.1021/acs.jpcb.7b10105
Ultrasensitive Microstring Resonators for Solid State Thermomechanical Analysis of Small and Large Molecules. Maximilian Karl, Peter E. Larsen, Varadarajan P. Rangacharya, En Te Hwu, Jukka Rantanen, Anja Boisen, and Thomas Rades. Journal of the American Chemical Society 2018 140 (50), 17522-17531. DOI: 10.1021/jacs.8b09034
Exploring the chemical space for freeze-drying excipients. Meng-Lund, Helena; Holm, Tobias Palle; Poso, Antti; Jorgensen, Lene; Rantanen, Jukka; Grohganz, Holger. In: International Journal of Pharmaceutics, Vol. 566, 2019, p. 254-263. https://doi.org/10.1016/j.ijpharm.2019.05.065
Recent work led to the founding of Zerion Pharmaceuticals ApS, dedicated to improve the solubility and bioavailability of poorly soluble drugs. The concept is based on a patented technology based on our research findings: Mishra, Jaya et al. “Whey proteins as stabilizers in amorphous solid dispersions.” European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences vol. 128 (2019): 144-151. doi:10.1016/j.ejps.2018.12.002
The SSP group is an active part in the Pharmaceutical Solid State Research Cluster and in the Nordic POP network.
Group members
Internal researchers
| Name | Title | Phone | |
|---|---|---|---|
| Search in Name | Search in Title | Search in Phone | |
| A L Carneiro Soares Do Nascimento | Guest Researcher | ||
| Alexander Svendsen | Laboratory Technician | +4535329782 | |
| Aliz Kispal | External | ||
| Amor Rayco Caceres Perez | Visiting PhD Student | ||
| Arlene McDowell | Guest Researcher | ||
| Bulut Bulduk | External | ||
| Daniele Musumeci | Guest Researcher | ||
| Francesca Terracina | Visiting Student | ||
| Grzegorz Sebastian Czyrski | PhD Fellow | +4535323722 | |
| Holger Grohganz | Associate Professor | +4535336473 | |
| Inês Catarina Batista Martins | Postdoc | ||
| Ji Zhou | Master Thesis Student | ||
| Jiajun Xie He | Master Thesis Student | ||
| Keyoomars Khorami | External, Ph.d Student | +4535331217 | |
| Korbinian Löbmann | External | +4535320541 | |
| Lara Sophie Sepke | Visiting Student | ||
| Manuel Gregoritza | External | ||
| Mireia Borras Vazquez | Visiting Student | ||
| Miriam Breunig | External | ||
| Per Piren Glæsner | External | ||
| Rikke Christine Albertine Helstrup | Master Student | ||
| Rong Di | PhD Student | +4591999558 | |
| Stephan Ta | External | ||
| Thomas Rades | Professor | +4535336032 | |
| Xuezhi Zhuo | External, Ph.d Student | +4591605400 |