Polymorph disappearance

Variations in lattice energies between amorphous and crystalline forms can significantly influence a drug s aqueous solubility, and increases of several hundredfold were observed for morphine and benzimidazole derivatives. Furthermore, a substance may exist in more than one crystalline form, such as chloramphenicol, dehydroepiandrosterone (DHEA), progesterone, sul-fathiazole, carbamazepine, cortisone, or prednisolone, to name a few. Polymorphic transformations, routinely observed for pharmaceuticals, are structural differences resulting from different crystal arrangements of molecules in the solid state. Although thermodynamic differences between polymorphs disappear once dissolved. 

It is a white, deliquescent solid, very powdery, which exhibits polymorphism on heating, several different crystalline forms appear over definite ranges of temperature -ultimately, the P4O10 unit in the crystal disappears and a polymerised glass is obtained, which melts to a clear liquid. 

The polymorphism of certain metals, iron the most important, was after centuries of study perceived to be the key to the hardening of steel. In the process of studying iron polymorphism, several decades were devoted to a red herring, as it proved this was the P-iron controversy. P-iron was for a long time regarded as a phase distinct from at-iron (Smith 1965) but eventually found to be merely the ferromagnetic form of ot-iron thus the supposed transition from P to a-iron was simply the Curie temperature, p-iron has disappeared from the iron-carbon phase diagram and all transformations are between a and y. 

Once the amorphous silica has nearly disappeared, the cristobalite that formed early in the calculation begins to redissolve to form quartz. The cristobalite dissolves, however, much more slowly than it formed, reflecting the slow rate of quartz precipitation. After about 300 000 years of reaction, nearly all of the cristobalite has been transformed into quartz, the most stable silica polymorph, and the reaction has virtually ceased. 

As introduced above, different forms of the same molecule can be observed in the solid state. The phenomenon is known as polymorphism, i.e., the concurrent presence of more crystal forms, only one of which is thermodynamically stable at a given pressure and temperature. However, more polymorphs can be observed simultaneously when kinetic conditions allow formation of metastable phases together with (or even in the absence of) the thermodynamically stable one. It might even occur that metastable phases are not recognized as such, simply because the most stable polymorph is (as yet) unknown. This might produce the extraordinary phenomenon of disappearing polymorphs [97]. 

It is important that the solid-state chemists keep a watchful eye on the possibility of disappearing polymorphs [92] and also of the well-known phenomenon of concomitant polymorphs which has been discussed recently [93], The generation of new polymophs via the addition of a meaningful choice of impurities in controlled amounts [93,94] is worthy of experimentation. 

Many other difficult questions arise when a situation described as a disappearing polymorph is encountered. Among them are Why did the new polymorph appear at all (often after years of no hint of its existence) Why does a previously robust process no longer yield the crystal form that had been obtained prior to the appearance of the new one What crystallization parameters must be modified to obtain either the old or the new form exclusively and robustly ... 

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