Crystal habit, solvent effect

Green, D. A., and P. Meenan. 1996. Acetaminophen crystal habit Solvent effects. In Crystal growth of organic materials, edited by A. S. Myerson, D. A. Green, and P. Meenan. ACS Conference Proceedings, pp. 78-84. 

The presence of a solvent, especially water, and/or other additives or impurities, often in nonstoichiometric proportions, may modify the physical properties of a solid, often through impurity defects, through changes in crystal habit (shape) or by lowering the glass transition temperature of an amorphous solid. The effects of water on the solid-state stability of proteins and peptides and the removal of water by lyophilization to produce materials of certain crystallinity are of great practical importance although still imperfectly understood. 

The work discussed in the previous paragraphs provides the framework for the prediction of crystal habit from internal structure. The challenge is to add realistic methods for the calculation of solvent and impurities effects on the attachment energies (hence the crystal habits) to allow this method to provide prediction of crystal habit. Initial attempts of including solvent effects have been recently described (71. 721. The combination of prediction of crystal habit from attachment energies (including solvent and impurity effects) and the development of tailor made additives (based on structural properties) hold promise that practical routine control and prediction of crystal habit in realistic industrial situations could eventually become a reality. 

Incorporation of Solvent Effects in Crystal Habit Calculations... 

Even though still in a prelinainaiy stage, it is hoped that this approach will result in a better solvent - effect corrector to the attachment energy calculations (IS) than the broken hydrogen bond model and a better fit of the predicted sucrose crystal habits with the observed ones. It is already clear that the present model can, at least qualitatively, distinguish between the fast growing ri t pole of the crystal and its slow left pole. 

Cocrystals are often prepared by a traditional solution crystalhsation approach such as solvent evaporation, coohng, or anti-solvent addition. There are a number of reasons for the popularity of the solution-based approach. Solution crystallisation can yield large, well-formed single crystals, from which one may easily evaluate crystal habit and surface features. Analysis of the diffraction pattern of a single crystal is typically the best means of obtaining an absolute crystal structure determination. Further, solution crystalhsation is an established and effective purification step. 

The nature of solvent has been found to have a profound effect on crystal habit of ibuprofen. Ibuprofen crystals precipitated from ethanol and acetone (solvents having high surface tension, dielectric constant, and less specific gravity) were thin, platy, and nearly circular-shaped, whereas those obtained from propylene... 

Garti, N. Karpuj, L. Sarig, S. The effect of solvents and crystallization conditions on crystal habit of cholesterol. Cryst. Res. Technol. 1981, 76(10), 1111-1115. 

Garti N, Leci CL, and Sarig S. The Effect of Solvents on Crystal Habit of 1,4-Di-Tert-Butylbenzene (DTB ). J Cryst Growth 1981 54 227-231. 

Changes in the solvent used or the presence of an impurity can also profoundly affect the crystal habit. Figure 2.17 shows the effect of aluminum fluoride on the habit of anhydrous calcium sulfate. The impurity transforms the needle-like habit to a cubic looking crystal. Figure 2.18 demonstrates the effect of urea on sodium chloride crystals. A large amount of qualitative information exists on the effect of impurities on crystal habit (Mullin 1993 ... 

Crystalline samples sometimes produce spectra with distorted band shapes, an effect known as the Christiansen effect [see Potts (1963) and Table 1.4]. Also, polymorphic forms of the same substance frequently show differences in infrared spectra. An example is N-benzoyl-2,3,4,6-tetra-0-benzoyl- -D-glucosylamine, a compound that exists in a form with melting point 113-115°C which, when heated to 117-120°C and allowed to crystallize from the melt, gives a form with melting point 184°C having a somewhat different spectrum in Nujol (Tipson, 1968). Also, different crystal habits (same melting point) of a compound may display partially differing spectra, especially if examined as mulls, in which little pressure is applied. Shifts of up to 20 cm" for certain bands have been observed (Barker et al., 1956) for crystalline and amorphous forms of some carbohydrates. In all such instances, however, spectra of samples of each of the forms, recorded after dissolution in the same solvent, or as a molten substance, are identical. 

A problematic area is how to ratify the effect of solvent or impurities. When analyzing the effect of solvent or impurities on crystal habit, two factors are essential to understanding the process. 

A detailed study on solvent effects relating to the growth of succinic acid crystals from water and isopropanol solutions was reported by Davey, Mullin and Whiting (1982). The faster growth of the (010) and (001) faces in water than in isopropanol resulted in a succinic acid habit modification from platelets to needles, as shown in Figure 6.36. Calculated a-factors for the two faces were found to be similar for both solvents, so the change of habit was considered to result from chemical interaction with the solvent. Succinic acid interacts, pre-... 

The solvent from which a material is crystallized can influence the crystal habit and growth rate. Bourne ascribes the effects of a solvem to two sets of factors one has to with the effects of solvent on mass transfer of the solute through adjustments in viscosity, density, and diffiisivity the second is concerned with the structure of the interface between the crystal and solvem. The analysis provided by Bourne concludes that a solute-solvent system having a high solubility is likely to produce a rough interface and concomitantly large crystal growfii rates. 

---