Drug dissolution & permeation
We have a strong interest in understanding the molecular reasons resulting in a poor aqueous solubility. We have contributed to the understanding of solid-state limited ('brick dust') versus solvation limited ('grease balls') solubility and established computational methods that predict, from molecular structure alone, the probability of a compound to be a 'brick dust' or a 'grease ball' molecule. These tools can guide the formulation scientists and/or medicinal chemists in successful development pathways for a particular compound, e.g. through re-optimization of chemical structure or formulation design.
Our research in the field of poorly soluble compounds is extensively based on studies using biorelevant dissolution media to predict e.g. intestinal solubility of drug-like molecules. We are now exploring the impact of food intake and contribution of formulation to the performance of the drug in vivo and have revealed molecular mechanisms of importance for solubilization in intestinal fluids. We are currently developing a virtual intestine to enable evaluation optimization of new dosage forms in the computer rather than making use of lengthy experiments, iteration of experiements or suboptimized animal studies.
The research team focuses on the development of sophisticated dosage forms that transforms problematic compounds (poorly soluble, biologics) into well-functioning oral medications. Different formulation strategies making use of lipid-based formulations, amorphous materials, mesoporous carriers and functionalized drug carriers are currently being explored, partly in the context of additive manufacturing and 3D printing to produce personalized medicines. Pediatric dosage forms to improve treatment and quality of life of severely sick children (cancer, neurological diseases, inflammatory bowel disease) are our main target within personalized medicines. The virtual intestine, computational pharmaceutics, enabling formulations and pediatric dosage forms projects are described below.