Berlin 2015 – wissenschaftliches Programm
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O: Fachverband Oberflächenphysik
O 83: Surface Chemistry and Growth
O 83.8: Vortrag
Donnerstag, 19. März 2015, 12:15–12:30, MA 144
In silico prediction of dissolution rates of molecular crystals — •Berna Dogan1, Julian Schneider1,2, and Karsten Reuter1 — 1Technische Universität München, Germany — 2QuantumWise A/S, Copenhagen, Denmark
Dissolution testing is not only helpful for quality control of drug formulations, but also provides important information for drug development e.g. to optimize the dissolution kinetics by admixture of pharmaceutically inactive excipients. At present, a rational optimization process is hereby limited by a lack of understanding of the underlying molecular processes during crystal dissolution. We contribute to this context with detailed kinetic modeling based on atomistic moleular dynamics (MD) simulations. Within a spiral dissolution model valid for low undersaturation the velocity of a retracting screw dislocation can be determined from the free energy of kink sites and the rate constant for the molecular detachment process of kink site molecules. We present molecular simulation protocols for both quantities [1,2] and use them to determine a macroscopic dissolution rate of the wide-spread excipient alpha lactose-monohydrate that is fully consistent with experimental rates obtained from single crystals. [1] J. Schneider, C. Zheng, and K. Reuter, J. Chem. Phys. 141, 124702 (2014); [2] J. Schneider and K. Reuter, J. Phys. Chem. Lett. 5, 3859 (2014).