Surface mediated polymorphic structures of drug molecules

New active pharmaceutical ingredients (APIs) often exhibit unfavorable low solubility and/or hindered dissolution behavior within an application relevant aqueous environment. As a result the therapeutic activity is diminished due to insufficient adsorption and bioavailability in-vivo which may even cause a rejection of highly potential APIs. The aim of this project is the solution based preparation and identification of surface mediated polymorphic crystal structures of APIs within thin solid films at substrate surfaces. Such polymorphs are distinct from other polymorphs which form in bulk solutions. They occur due to interactions with the surface on account of altered boundary conditions; variations in Coulomb, Van der Waal or H-bonding interactions results in surface mediated structures during crystallization. In addition, the kinetic of the crystallization is of importance as a fast crystallization favors the assembling into surface mediated polymorphs. In general, the solubility of materials strongly depends on the polymorphic structure, as different crystal facets provide altered surface energies. The introduction of surface mediated structures is expected to alter the solubility and the dissolution properties significantly providing new routes for pharmaceutical formulations. Within the project fundamental interactions of API molecules with surfaces will be identified. Adsorption studies of various API molecules at liquid solid interfaces will be performed by in-situ quartz crystal microbalance measurements. Variations of solvents and surfaces will highlight correlations of the surface access/kinetic of the adsorption or desorption process and the boundary conditions. Solution based deposition techniques like spin coating and drop casting will be applied to obtain thin and solvent free API layers on various surfaces which will be investigated by state of the art microscopy or X-ray based techniques. Changes in the process conditions (rotation speed, concentration, evaporation time of the solvent, ) will provide sufficient variability to identify important parameters for the formation of surface mediated polymorphic structures. Standardized dissolution testing with USP apparatuses will provide information on altered dissolution properties with respect of standard preparation routes. The knowledge on the formation of surface mediated structures will be used to prepare defined thin layers of API on nanoparticle surfaces which are usable within pharmaceutical relevant formulations.

No additional funding sources recorded.