Polymorphs formation

It is important to have an understanding of the competing thermodynamic and kinetic factors that govern crystallization. Situations exist where one polymorph formation is kinetically controlled, while another is thermodynamically controlled. 

The effects of different rates of cooling down to isothermal crystallization temperature, different crystallization temperatures and different rates of heating during melting, on polymorph formation and transformation are easily studied by DSC. However, it is not possible unequivocally to identify polymorphs by DSC this must be done by X-ray diffractometry (Rossell, 2003 see below). 

When using glyceryl monostearate in a formulation, the possibility of polymorph formation should be considered. The a-form is dispersible and foamy, useful as an emulsifying agent or preservative. The denser, more stable, p-form is suitable for wax matrices. This application has been used to mask the flavor of clarithromycin in a pediatric formulation. ... 

Trace amounts of impurities can lead to the formation of a new crystalline form or the preferential formation of another polymorph, as discussed for crystallization of abecarnil. For this reason it is wise to screen for polymorph formation using both highly purified final product and material of routine purity. The solids resulting from the removal of solvents from a final product extract may be appropriate for polymorph screening. 

When compared to the development of models and methods for other unit operations, it is obvious that crystallization has not been generalized to the degree that has been accomplished for distillation, extraction, adsorption, etc. This situation is changing rapidly, however, with increasing research now being carried out at academic and industrial centers on CrystaUization fundamentals to model and predict nucleation and/or growth rates as well as other key properties, including polymorph formation. 

Curves F-G and H-G represent two different modes of carrying out crystallization by cooling and would be expected to result in two very different results in terms of physical properties—mean particle size (mean dp) particle size distribution (PSD), surface area, and bulk density, as well as possible differences in rejection of impurities and occlusion of solvent. Other differences can include a change of morphology and a potential for changes in polymorph formation. These differences result from the supersaturation and surface... 

The majority of the crystallization literature deals with inorganic crystals, and the organic chemistry literature mainly covers small organic molecules with few degrees of freedom such as glutamic acid, phenytoin, or paracetamol. The reality in the pharmaceutical industry is often much more complicated— molecular weights above 1000 g/mole are common, and complex molecular structures have an effect on nucleation and growth kinetics as well as on the likelihood of polymorph formation. 

R.K. Layek, S. Samanta, D.P. Chatterjee, and A.K. Nandi, Physical and mechanical properties of poly(methyl methacrylate) -functionalized gra-phene/poly(vinylidine fluoride) nano composites Piezoelectric p polymorph formation. Polymer, 51 (24), 5846-5856, 2010. 

There are no solid-phase transformations such as polymorphism, formation of solid solutions and compounds, and azeotropy in liquid-gas equilibria in the systems under consideration. 

Zhong G, Zhang L, Su R, Wang K, Fong H, Zhu L. Understanding polymorphism formation in electrospun fibers of immiscible poly(vinylidene fluoride) blends. Polymer 2011 52 2228-37. 

DCPA inhibits the growth of grass species by dismpting the mitotic sequence, probably at entry (190). DCPA influences spindle formation and function (181) and causes root-tip swelling (182) and britde shoot tissue (191). It has been reported that DCPA, like colchicine and vinblastine, attests mitosis at prometaphase and is associated with formation of polymorphic nuclei after mitotic arrest (192). Pronamide also inhibits root growth by dismpting the mitotic sequence in a manner similar to the effect of colchicine and the dinitroanilines (193,194). Cinmethylin and bensuhde prevent mitotic entry by unknown mechanisms (194). 

Oxides. Owing to the importance as nuclear fuel material, actinide oxides have been intensively investigated. These are very compHcated compounds because of the formation of non stoichiometric or polymorphic materials. Actinide oxides are very heat-resistant and Th02 is the highest... 

In some cases there is evidence of multiple solid-solid transitions, either crystal-crystal polymorphism (seen for Cl salts [20]) or, more often, formation of plastic crystal phases - indicated by solid-solid transitions that consume a large fraction of the enthalpy of melting [21], which also results in low-energy melting transitions. The overall enthalpy of the salt can be dispersed into a large number of fluxional modes (vibration and rotation) of the organic cation, rather than into enthalpy of fusion. Thus, energetically, crystallization is often not overly favored. 

The ability of triphenylphosphine to act as a reducing agent probably involves initial formation of Ph3PCl2, which then undergoes solvolysis. If the synthesis is carried out using a small volume of ethanol, an orange polymorph is formed [45]. 

---