(410e) Solution Speciation Of Impurities: A Force Field Simulation Of Its Impact On α-Glycine Crystal Habit

Solution crystallization of small organic molecules is of central importance to industrial manufacturing of food, pharmaceuticals and specialty chemicals. It is requisite that the particulate products obtained from the crystallization process have desired solid state properties such as shape (crystal habit), form (crystal structure) and size distribution. These properties, in turn, impact the downstream processing and formulation of the final product. In industrial systems, it is not uncommon that impurities, whose molecular structures are similar to the primary solute, come from the upstream processes. From previous studies, it is known that this class of impurities interacts with a developing crystal resulting in habit modification and crystallization of unexpected polymorphs. Isomorphic impurities also form solid solution in the crystalline state and affect crystal purity and solubility (Koolman and Rousseau 1996). Alternatively,″tailor-made″ additives can be used to alter crystal growth kinetics and therefore achieve the desired crystalline properties. Recent studies are focused on theoretical simulation of impurity effects on the crystal growth process. In this work, we have used glycine (a simple amino acid) as the primary solute, and selected higher homologous α-amino acids as the impurities. Glycine is usually crystallized from pure aqueous solution as the metastable α-form. On the basis of this fact, initially, we have used atom-atom potential energy calculations to predict the theoretical crystal habit of α-glycine from its crystal structure (Materials Studio Modeling,Accelrys Software Inc.). The morphologically significant crystal facets were identified by comparing the experimental crystal habit with the one simulated. Subsequently, specific crystal surfaces were cleaved from the optimized α-glycine crystal structure and then built as a superstructure. The adsorption of impurity molecules that exist as zwitterions and anions was modeled by making a stereospecific docking on these crystal surfaces. Preferential interaction of impurity molecules with the glycine crystal, and the subsequent inhibition of crystal growth were quantitatively determined through ″layer″ and ″attachment energy″ calculations. The sensitivity of these calculations on the force field parameters was also investigated. The results obtained are compared with the experimentally observed habit modification (Poornachary et al. 2007). References Koolman, H. C. and Rousseau, R. W. ″Effects of isomorphic compounds on the purity and morphology of L-Isoleucine crystals″ AIChE J., 42 (1), 147 (1996) Poornachary, S. K., Chow, P. S., Tan, R. B. H. and Davey R. J. ″Molecular speciation controlling stereoselectivity of additives: Impact on the habit modification in α-glycine crystals″ Crystal Growth & Design,7 (2), 254 (2007)