Crystal Morphology Prediction

C. HP Morphology is an advanced method for predicting crystal morphology for salts and solvates. 

Some reported examples of the use of PBC analysis to predict crystal morphology include hexamethylenetetramine (Hartman and Perdok, 1955), calcium sulphate (gypsum) (van Rosmalen, Marchee and Bennema, 1976), anthracene (Hartman, 1980), magnesium hydrogenphosphate (newberyite) (Boistelle and Abbona, 1981), sodium sulphite and potassium sulphate (Follner and Schwarz, 1982), succinic acid (Davey, Mullin and Whiting, 1982), sucrose (Aquilano et al, 1983). 

Schmidt, C. (2012) Predicting crystal morphology grown from aqueous solution. PhD thesis. Martin-Luther-Universitat Halle-Wittenberg. 

With a simple construction, the predicted crystal morphology is established as explained in Fig. 13.12 (right), using expansion vectors whose direction is determined... 

As predicted, the presence of cinnamic acid in solution caused cinnamide to crystallize as flat prisms with prominent 011 faces (Figure 4b). The crystal morphology was modified along c by the use of amide additives that contain a bulky Cl substituent at the a- or P-carbons of cinnamide. When replacing a substrate molecule, these additive molecules interfere with the deposition of the next Oil layers (Figure 3), yielding 011 platelike crystals (Figure 4d). 

The more modern methods of predicting the morphologies of crystals are based on the calculation of the energies of the various faces. The methods are based on the intuitive consideration that the closed polyhedron describing the shape of the crystal is determined by the faces with the lowest surface free energy and that the extension of these faces is inversely proportional to the respective surface free energy. 

Knowledge of crystal morphology and ways to control and predict the morphology of drugs and excipients could prove invaluable in formulation and product... 

The AE method has been used to successfully predict the morphology for many molecular crystals, especially those that are dominated by strong anisotropic forces. In the case of carbamazepine dihydrate, which is dominated by intermolecular hydrogen bonding (especially along the Z -axis), this model predicts a morphology much closer to the observed morphology (Fig. While this method can account for... 

Morphology predictions based on the AE method also assume that crystals are grown in vacuo, i.e., in the absence of solvent. Consequently, the solvent effects on morphology are ignored using this method. Roberts and coworkers have developed a method that calculates a modified AE which can be used to predict the effects of solvents as well as other additives on crystal morphology.f " ... 

Clydesdale, G. Docherty, R. Roberts, K.J. HABIT-a program for predicting the morphology of molecular crystals. 161. Comput. Phys.Commun. 1991, 64, 311-328. 

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