Solid State Pharmaceutics
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.
Amino acids as co-amorphous stabilisers for poorly water soluble drugs - Part 2: Molecular Interactions
Korbinian Löbmann, Riikka Laitinen, Clare Strachan, Thomas Rades and Holger Grohganz
European Journal of Pharmaceutics and Biopharmaceutics 85 (3B), 2013, 882-888
The glass transition temperature of the β-relaxation as the single predictive parameter for recrystallization of neat amorphous drugs
Eric Ofosu Kissi, Holger Grohganz, Korbinian Löbmann, Michael T. Ruggerio, J. Axel Zeitler and Thomas Rades
Journal of Physical Chemistry B 122, 2018, 2803-2808
Amorphization within the tablet: Using microwave irradiation to form a glass solution in situ.
Maria Doreth, Murthada Hussein, Petra Priemel, Holger Grohganz, Rene Holm, Heidi Lopez De Diego, Thomas Rades and Korbinian Löbmann.
International Journal of Pharmaceutics 519, 2017, 343-351
Staff at Solid State Pharmaceutics Group
Group leader: Holger Grohganz