| OBSERVATION'S |
When polymorph conversion occurs, it may be impossible to reproduce the less stable form. It just disappears. Tales of disappearing polymorphs abound. Evelyne Chassagneux, director of business development at Archemis, a French contract development organization, recalls a drug candidate for which Phase I clinical trials had just been completed when a new polymorph appeared. "The properties changed, and we never recovered the old form. Fortunately, the conversion occurred at an early stage in development. "The lost form was not registered. If it had been registered, all the work would have had to be redone. That would have been a disaster."
Furthermore, in this case, the late-appearing polymorph fortuitously had better processing qualities. "The old crystals were needlelike, very sticky, with lots of static electricity," Chassagneux says. "The new form was easier to formulate." Despite the compelling case for polymorphism studies early in drug development, the practice is not standard in the pharmaceutical industry. "There are two types of companies," Chassagneux says. "Those that have already experienced problems do the studies very early. They have learned their lesson. The others don't pay attention. When they have problems, they ask us to troubleshoot."
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