(83e) Influence of Additives On Crystal Morphology of Organic Molecular Crystals

Crystal morphology has a great impact on the end-use efficacy of solid products as well as on the downstream performance of the entire manufacturing and formulation process. Foreign molecules like additives or impurities influence the crystal morphology to a significant extent by inhibiting the growth mechanism of certain crystal faces. The additives can be byproducts of the preceding step of reaction or they could be specially designed to obtain specific crystal morphologies for focused applications, for example, using crystal growth inhibitors to reduce the size of kidney stones[1].

Because of the specific chemical structure of structurally similar additives, they can incorporate or lock into the original lattice only in certain configurations, hence only some of the crystal faces can recognize these additive molecules. Once attached, they interfere with the first turn of a rotating growth spiral and hence slow down the growth rate of the face [2].  In this work, we develop a generic probabilistic scheme for quantitatively estimating imposter recognition on each crystal face using a combination of mean field theory and energy minimization. Based on this recognition, the mechanistic effect of impurity on the first turn of the spiral and hence modified growth rates and modified crystal habits are computed. These concepts are generalized for all molecular crystals, including non-centrosymmetric molecules. Finally, we present work on specific systems of immense industrial and scientific interest such as  paracetamol/PAA[3] and L-cystine/L-CDME[1] and compare our results with experiments from the literature and our laboratory.

References:

[1]: Rimer J . D, et al, Science 330, 337(2010)

[2]: Sizemore J.P. and Doherty M.F,  Cryst. Growth Des., 9,6 (2009)

[3]: Chow et al, Intnl. Journal of Pharmaceutics, 24 (2-3) (1985)