Examples of the Selective Preparation of a Desired Crystal Modification by an Appropriate Choice of Operating Parameters

If a compound can crystallize in more than one structural modification, this will generally also be manifested as different morphologies. In a manufacturing process crystal morphology can have a decisive impact on product characteristics such as filterability, drying time, flowability, etc. In addition, it is usually one particular modification that undergoes registration. In this lecture transcript, two examples of the influence of operating parameters on the obtained crystal modification are presented. The first example comprises a food colorant for which four crystal modifications are known. The conventional operating procedure always yielded modification D, which is characterized by extremely poor filterability. Systematic investigations have shown that in suspension each crystal modification is stable within a narrow temperature range. After solid−liquid separation no interconversion of the crystal modifications occurs. Through an appropriate change to the manufacturing process it was possible to reliably obtain modification C, the filterability of which is 30% higher than that of modification D. The drying time was also reduced by a half. The second example comprises a pharmaceutical active substance that can crystallize in one of two modifications, A and B, with B being the modification that has been registered. In the manufacturing process the product was obtained from a reaction in ethanol, and crystallized as modification A, with the desired modification B subsequently obtained by recrystallization from n -butanol. To avoid the costly recrystallization and extremely lengthy drying of the butanol-moist crystals, the goal was to obtain modification B from ethanol directly. It was found that it is not only the solvent used that determines which modification is obtained but that modification B can also be obtained through a thermal interconversion at 70 °C. This transformation is most simply achieved during drying.