The research focus of the working group is on the development of strategies for the administration of poorly soluble drugs, in particular with the aid of nanoparticulate drug delivery systems. We are also working on pellets for the administration of poorly soluble drugs in individualized dosage forms. Another research area is concerned with formulation development for therapeutic biomacromolecules.
Nanoparticulate drug delivery systems
Of particular importance in our research into the development, production and characterization of nanoparticulate drug delivery systems for the formulation of poorly soluble drugs is the question of structure-function relationships in these systems. The main focus is on the stability, the drug carrier capacity and the release properties of the formulations as a function of their composition, the manufacturing process and their ultrastructure. Based on this, new strategies for systems with optimized carrier properties, controlled release and processes for their production are being developed. The aim is to enable the targeted construction of nanostructured application systems in the future.
We primarily use lipid-based nanoparticulate systems (solid lipid nanoparticles, emulsion systems and dispersions of liquid crystalline phases) to process poorly soluble drugs, especially into injectable dosage forms, which are always comprehensively characterized. Among other things, the effects of pharmaceutical process steps (e.g. dispersion processes, sterilization) on the properties of the carrier particles are investigated. With premix membrane emulsification, we have been able to establish a method that enables the production of colloidal dispersions with a particularly narrow particle size distribution and production on a very small scale. In the past, fundamental findings on the crystallization and thermal behavior of lipid nanoparticles as a function of their composition and particle size have been developed, which open up interesting possibilities for modifying the interaction with active ingredients.
Pharmaceutical carrier systems must have an appropriate drug carrier capacity, which we are evaluating for various nanoparticulate systems. The longer-term goal is to identify suitable carrier systems that save as much material as possible and are also based on theoretical concepts. In addition to the question of which carrier system is the best formulation solution for a given active ingredient, we are also looking at the effects of the active ingredient on the properties of the particles. In order to be able to carry out this work more efficiently in future, we have developed a screening process for investigating the loading capacity. This is used both to find formulations for newly developed drug candidates and to address fundamental questions, e.g. the localization of active ingredients in the particles.
Our work on drug release is aimed at realistically assessing the potential of nanoparticulate carriers and developing improved strategies for controlling drug release. Fundamental release mechanisms are to be worked out and improved carrier systems developed on this basis. As no reference method for investigating the release properties of colloidal drug delivery systems exists to date, we are comparing different approaches in order to develop suitable methods on this basis. We are increasingly taking the physiological situation into account. With regard to the interactions of lipid nanoparticles with biological model systems, primarily with regard to their parenteral application, we are particularly interested in the effects of the composition, particle shape and size as well as the surface properties of the particles.
Drug nanoparticles are an important alternative for the processing of poorly water-soluble active ingredients. There are a number of open questions regarding the stabilization of the particles during and after production and the preservation of the nanoparticulate state during further processing steps. We are investigating these questions in cooperation with the Institute for Particle Technology. As the focus here is on peroral administration, not only liquid nanoparticle suspensions are of interest, but also methods for converting them into solid forms.
Formulations for therapeutic biomacromolecules
In this area, we are working on the development and characterization of injectable/implantable formulations for controlled protein release. We are also concerned with strategies for the administration of therapeutic biomacromolecules (proteins, RNA) using lipid nanoparticles, including in a collaborative project with a number of working groups at the PVZ, Hannover Medical School, Leibniz Universität Hannover and several Fraunhofer Institutes.
Pellets for patient-individualized drug therapy
In the context of research into the development of pellets for patient-individualized drug therapy, self-dispersible lipid and hydrogel-based pellets are being produced, the latter being loaded with lipid nanoparticles. Manufacturing methods include melt-extrusion on the one hand and extrusion dripping, usually by means of laminar jet breakup, on the other. The aim of these systems is to increase the oral bioavailability of poorly water-soluble active ingredients. The pellets produced are intended for use in a patient-individualized capsule with the aim of improving adherence in the context of polymedication. As part of the fundamental research, the influences of the composition and the process parameters on the pellets are analyzed.
Publications from research group Bunjes