Common Methods Used for Examination of Solid Forms

This serves as an example of the extremes one can go if one tmly wants to better understand the process and the form of the compound in the product. This approach is less important for detecting polymorphic form conversion in the solid state, since polymorphic solubility typically varies by less than a factor of two and tablets at very low strength would generally be classified as a type one by the biopharmaceutical classification system. In addition, polymorphs rarely have pronounced differences in chemical stability. On the other hand, if a compound is somewhat unstable and significant amount of amorphous material is potentially present, this approach can be used to determine if it is responsible for drug instability in the tablet formulation. In any event, this reference serves as a very good example of the strength of a powerful approach that has not been widely applied in our industry. 

5 COMMON METHODS USED FOR EXAMINATION OF SOLID FORMS 

TABLE 12.2 Common Solid-State Techniques and Approximate Sensitivities to Physical Forms 

Physical Form X-ray Powder Diffraction LOD LOQ (%) Solid-State NMR Spectroscopy LOD LOQ (%) IR/Raman Spectroscopy LOD LOQ (%) 

True polymorphs Unique diffraction peaks. Useful for determination of phase purity and percentage crystallinity 0.5-2 Unique chemical shifts. Useful for determining phase purity, molecular mobility 0.5-5 Characteristic spectra, sensitive to H-bonding 5-10 

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