Thus, comparison of the diffraction pattern of the drug substance to the calculated pattern provides a direct method of identification of the substance. It is important to point out that an identification test is not a limit test. That is, a visual comparison of the spectrum or diffraction pattern of a drug substance to that of a reference merely provides an identification of the substance and does not quantify its polymorphic purity. In recent years, the term polymorphs is frequently used to describe polymorphs, solvates, amorphous forms, and desolvated solvates. Mixtures of polymorphs should be avoided if possible.
Mixtures are sometimes indicative of lack of control in the production process.
Thus, careful optimization of the production process, in general, and the final crystallization process, in particular, are needed to avoid mixtures. If it is impossible to avoid mixtures, research should be conducted to establish a best effort attempt to achieve polymorphic purity. In cases where the polymorph affects bioavailability or chemical stability, there is a developing interest in setting specifications for drug product. Of course, methodology must be available to determine the polymorphs present in the drug product. Importantly, the detection limit is usually higher in drug products since the excipients often interfere with the assay.