Crystallization of polymorphs

In the previous section the emphasis was on the variety of different crystallization techniques that have led to concomitant crystallization of polymorphs. In this section we survey the additional diversity of chemical entities which have exhibited this phenomenon, since such diversity can also provide guidelines to developing methods for controlling the polymorph obtained. 

To this point this account of instances of concomitant polymorphs has been phenomenological. We have discussed the thermodynamic and kinetic crystallization of polymorphs. There is still the question if any insight concerning controlling the polymorph obtained can be gained from the study of the crystal structure of concomitantly crystallized polymorphs. A qualitative attempt was made to see if details of the... 

Questions on the transferability of crystallization microtechniques to larger scale processes that are reproducible require careful consideration and study of crystallization kinetics. While operationally useful variables that describe crystallization methods are often related to crystallization outcomes, this approach lacks meaningful information for developing a process that yields reliable outcomes because the factors that determine the crystallization kinetics and outcomes are not explicitly considered. For instance, compare the following two approaches to describe the processes for the selective crystallization of polymorphs ... 

Koshkhoo S and Anwar J. Crystallization of Polymorphs The Effect of Solvent J... 

Threlfall T. Crystallization of Polymorphs Thermodynamic Insight into the Role of Solvent. Org Process Res Dev WOO, 4 384—390. 

Khoshkhoo S, Anwar J. Crystallization of polymorphs the effect of solvent. J Phys D Appl Phys 1993 26 B90-B93. 

Addition of GeC>2 enabled the first synthesis of pure polymorph C of zeolite Beta (ITQ-17 [11], Fig. 3), which was predicted by Newsam et al. [40] but also of a new family of related materials (like ITQ-16), in which the ratio of polymorphs A, B, and C can be varied [41] (in zeolite Beta polymorphs A and B are in the ratio 60 40). The structure-directing role of the Ge02 in the synthesis of polymorph C has been clearly demonstrated. Fig. 4 depicts a SEM image of the crystals of polymorph C. A number of different templates (from both the structural and sterical points of view) was tested under the same hydrothermal conditions (temperature range 135-175 °C, 15-120 h, Si/Ge 0.5-30) and in all cases pure polymorph C was synthesized despite the fluoride or hydroxide medium employed. However, in the absence of germanium zeolite Beta, with a typical intergrowth of polymorphs A and B, ZSM-12 or ITQ-4 were produced [11]. 

The general considerations above highlight the importance of nucleation and the role of environmental conditions (e.g. solvent, temperature) in the crystallization of polymorphs as well as their interconversions. These areas continue to be the subject of intense interest especially in the context of polymorphic control in crystallization. 

In the crystallization of polymorphs influence with some special additives is observed(i-3). Such effect is due to the relative change of nucleation rate and growth rate of the polymorphs, the effect also contains the change in transformation rate(4,5). Furthermore, a morphological change occurs in many cases. On the other hand, a crystallographic approach has been applied to effect of various type of additives on crystal growth(6-fl). However, the effect of additives espeddly on the kinetic behavior of polymorphism has not usually been treated quantitatively and the mechanisms are not known. 

This volume contains 23 chapters organized in five sections. More than a third of the cluq)ters deal with the crystallization of polymorphic compounds that can crystallize in more than one form and the crystallization of chiral compounds. This emphasis is a reflection of die current int st in these two fields. The other four areas are basic studies, smdies related to industrial crystallizers and processes, and two areas involving crystallization of particular organic and inorganic compounds. A diif nt organization of the book would have shown that 10 of the papers deal with aspects of crystallization of proteins, amino acids, and pharmaceuticals, a sign of the increased activity in this area of crystallization. 

The choice of solvent plays an important role in the crystallization of any substance. Properties of the solvent such as hydrogen-bonding capability, polarity, dipole moment, boiling point, dielectric constant, viscosity, density, and so on influence the crystallization of polymorphs. Fnrthermore,... 

Kawashima Y, Lin SY, Oj wa M, Handa T, Takenaka H. Prep>arations of agglomerated crystals of polymorphic mixtures and a new complex of indomethacm-epirizole by the spherical crystallization technique. J. Pharm. Sci. 1985 74,1152-6. 

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