Four widely-used computational methods have been developed for the morphology prediction: (i) The Bravais Friedel Donnay Harker (BFDH) method is a geometrical approach that analyzes crystal lattice and symmetry and generates a list of possible growth faces and their relative growth rates, from which the crystal morphology can be deduced. (ii) The Attachment Energy method calculates the energy released when a growth slice is added to a growing plane. The growth rate of the face is proportional to its attachment energy. Faces with the lowest attachment energies are the slowest growing and, therefore, have the most morphological importance. A Wulff plot is then constructed from the energy calculation, producing the final morphology. (iii) The Surface Energy method predicts the morphology based on the total surface energy of a crystal to be minimized. The theory behind is the argument by J. W. Gibbs that the morphology is determined by the minimum of the surface free energy for a given volume and temperature. (iv) The Hartman-Perdok method provides a systematic way to generate stable growth planes of a crystal. It removes one of the assumptions of the Attachment Energy method, namely, the growth planes are always ideal and flat. Once the stable growth planes have been identified, the Attachment Energy method is used to calculate the growth morphology. Energy calculations in these methods are typically done with empirical models or force fields.
Effects of additives on growth morphology have been closely examined by Lahav, Leiserowitz and co-workers. They have demonstrated using “tailor-made” or structurally similar additives to control crystal morphology and hinder the growth. These additive molecules typically have a similar framework to the host molecule with one functional moiety altered. It has been proposed that additive molecules adsorb and replace host molecules on crystal surfaces due to similar molecular shapes. Depending on the orientation of altered moieties, growth of host molecules to specific faces may be hindered, leading to a different morphology. The role played by additive is elucidated based on molecular shape and geometry hindrance in terms of adsorption site and orientation of altered functional moieties. Yet, we have shown in our earlier work that appearance of a new face of acetaminophen single crystals by using a tailor-made additive could not be explained based on the geometry hindrance. We suspected the surface reconstruction due to unique additive-surface interactions led to the morphology change.