Selection of Optimal Form for Development

As stated in Section 5.1, all solid-state properties of different polymorphs will be different. Which of these parameters is of special importance for a particular type of industry and a particular application can vary. While color is probably the most important parameter of a pigment, taste and feel are decisive for foods, density for explosives, solubility, processability and stability in the pharmaceutical industry, and so on. In any case, it is imperative for aH industries that all possible forms are known and characterized, since the unexpected appearance of a new form may have very serious consequences. An example for that is the well-known Norvir Case [30], where the thermodynamically stable form was found only long after the product was on the market. Subsequently, the original metastable form could not be produced anymore and a new formulation for the product had to be developed [31] causing very high costs. 

In the pharmaceutical industry, often stability is the overriding factor so, in most cases, the stable polymorph or a hydrate will be chosen for development. As outlined in Section 5.3, the stable form has the normally undesired property of being the least soluble one, but that is often considered a smaller problem than the potential conversion of a metastable form to the stable form during storage. If hydrates exist, the decision becomes more diSicult, since the thermodynamic stability then depends on humidity. Knowledge of the critical water activity, the kinetics of conversion, the conditions of use, and so on are then crucial in order to be able to select the optimal form. 

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