Show description

It is important to remember that XRPD patterns which differ in appearance do not necessarily represent different crystalline forms, since the patterns can be greatly affected by sample size and preparation, which cause preferred orientation. When the XRPD patterns have been organized, samples exhibiting each of the pattern types should be analyzed by other methods, such as DSC, TGA, IR spectroscopy, Raman spectroscopy, or solid-state NMR spectroscopy. The data resulting from these analyses can often be used to determine types of solid forms represented by samples exhibiting different XRPD patterns.

Free acid Calcium Unsolvated Pentahydrate 8/3 Hydrate Pentahydrate Heptahydrate Decahydrate Trihydrate Heptahemihydrate Pentahydrate A Pentahydrate B Heptahydrate Octahydrate 31 34 Magnesium Sodium Zinc 32 35 33 IV. SOLID FORM SELECTION It is obvious from the preceding discussion that salt and solid form selection are intertwined. The propensity of a compound, either neutral or a salt, to exist in different crystal forms is considered as part of the salt selection process. However, once selected for inclusion in drug product, the solid-state properties of a given compound must be evaluated in detail.

The practical result is that a kinetically favored but metastable crystalline form of a new compound can exist alone for long periods of time (often years) because seeds of a more stable form are not present. However, once a seed of the more stable form arises, crystallization of that stable form can begin and all of the existing metastable material can, and eventually will, be converted to the stable material. Once a given polymorphic form has crystallized, its seeds are everywhere, and it can be difficult to remake original forms.