Color crystalline, polymorphic forms

A specific polymorph may be absolutely essential for a crystalline product, for example, one polymorph may have a more desirable color or greater hardness or disperse in water more easily than another polymorph. Often, one polymorphic form is more stable than another (for example, at 80°C the orthorhombic I form of ammonium nitrate is more stable than the trigonal form) at conditions to which a product is exposed. An interesting approach to... 

Amylose. A component (20-30%) of starch surrounded by amylopectin. A. is a linear a-l,4-glucan, Mr 50000-200000 (see figure at starch). Crystalline A. occurs in various polymorphic forms (A, B, C, and V-A.), that differ in conformation and crystal packing. A. is soluble in water and gives the characteristic blue color with iodine-potassium iodide solution (Lugol s solution) (formation of inclusion compounds, traces of iodide ions are necessary for occurrence of the blue color, formation of I5 ions I -1 I I -1). Because of its predominately unbranched structure, A. can be degraded to oligosaccharides both by a- and by /S-amylase. The screw-like (helical) conformation also allows the formation of inclusion compounds with alcohols. 

When different configurations of the same molecule crystallize in separate crystalline forms, they are termed as configurational polymorphs. As a caveat, since configurational isomers can be considered to be separate chemical entities, these solids may not be strictly classified as polymorphs. Yet another classification of polymorphs that is closely related to confignrational polymorphism is tautomeric polymorphism which occurs when different tautomers of a compound exist in different polymorphs. There are cases where confignrational isomers or tautomers can interconvert in solution, and the fact that their relative population and stability depends on factors such as temperature, solvent, pH, and so on makes them appear as different crystalline polymorphs. In contrast to other, previously described classes of polymorphs, tautomeric polymorphs are rare. An early report of tautomeric polymorphism by Desiraju is the compound 2-amino-3-hydroxy-6-phenylazopyridine, which exists as hydroxyazo and quinonehydrazone crystals of different colors. Polymorphs of the antiulcer drug omeprazole (Figure 6) also represent tautomeric polymorphs that were characterized by SC-XRD. ... 

Figure 3-9. (a) Powder XRD of crystalline dimethyl fuschone 6 shows a mixture a (80%), /3 (18%) and y forms (2%) at 30°C. (b) Heating the concomitant mixture to 170°C shows pure /3 form in >97% polymorphic purity from PXRD match with the simulated powder profile from the X-ray crystal structure (see color plate section)... 

You might wonder why the existence of different polymorphs of a pharmaceutical compound is of concern, given that the same molecules comprise the polymorphs. Answers to this question arise from the fact that different crystalline forms of a compound may have different physical properties, such as color, melting points, and solubilities. For example, acetaminophen (Tylenol ) is known to exist in at least three different crystalline forms, two of which are pictured below. Form I is a monoclinic prism, the form usually obtained by recrystallization of acetaminophen from water it melts at 169-172 C. Form II, an orthorhombic form, is thermodynamically less stable than Form I and can be formed by rapidly cooling pure molten acetaminophen followed by warming the resulting super-cooled liquid to about 80 °C (see Kauffman, J. F. Batykefer, L. M. Tuschel, D. D. J. Pharm. Biomed. Anal. 2008, 48, 131-1315). Its melting point is 158-160 °C. It is this form that is desired for use in the pills you can buy because its crystal structure turns out to be more suitable for compression into tablets than is Form I. 

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