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"We're focusing our effort on the API," Myerson says. "That includes polymorphism, crystal shape, crystal size, understanding what data are required on a very small scale to make the same material repeatably on a larger scale, interaction of API with excipients, and how unit operations--such as granulation, compaction, and tableting--affect crystal structure."
The center is funded by subscriptions from member companies, which at present number three: Abbott, Aventis, and Bristol-Myers Squibb, Myerson says. Currently, three projects are under way: developing methods for seeding, evaluating techniques for online sensing of crystallization parameters, and studying the interaction of APIs with excipients. DRUG COMPANIES have urgent reasons to systematize knowledge in these areas, Myerson says. First, the Food & Drug Administration has become very strict about API form, shape, and size distribution, especially after the generic drug scandal of the late 1980s. Patients taking some generic drugs were not getting the therapeutic effect because the API in the generic version was a different polymorph and had poorer solubility and bioavailability than that in the brand-name drug.
Second, mistakes can cost hundreds of millions of dollars.
Ritonavir is well-known, but many other cases of new polymorphs appearing at late stage are not made public, Myerson says. "It is very expensive to go back, reformulate, and do your testing again."
Companies constantly have scale-up problems, often because they haven't done the correct experiments on a small scale and they don't have the appropriate fundamental data for developing a crystallization process, Myerson says. "It's shocking sometimes, but drug companies have so many precandidate compounds that the strain in getting data early has led them to not get as much. When suddenly one of these compounds becomes hot and they have to make more of it, they go without basic data."
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