You follow the recipe to the letter, purchasing the recommended brands listed, using a thermometer to ensure your oven is calibrated, etc. But when you go to pull it out of the oven, you find it’s not a pie at all—it’s a cobbler. Confused, you call a friend who’s made the recipe before and gotten great results.
She bakes the pie again and encounters the same problem—a mysterious cobbler where a pie should be. Then you both call a friend who made the pie just the other day, he brings the pie over to show it off, but after talking for a while, you discover it’s also turned into a cobbler. And yet this exact scenario happens in drug manufacturing with alarming frequency.
Pharmaceutical manufacturers will follow a known process for creating a drug, but during the crystallization process, a slightly different version (or polymorph) shows up. It may have the same chemical formula, but this new polymorph has a slightly different shape that gives it dramatically different properties. And the really spooky thing is that the new polymorph isn’t confined to any single lab, anyone who tries to make the first polymorph will find that it has simply vanished.
In some cases, even bringing the old polymorph to a lab that’s made the new polymorph is enough to make that product transform as well. It’s as if the specific chemical product were erased from the planet by some supernatural force. Perhaps the most famous disappearing polymorph was the antiretroviral ritonavir created by Abbott Laboratories and approved in 1996 for the treatment of HIV/AIDS.
Form I of the drug was sold in gel capsules but then it got superseded by Form II in 1998. This form, which had the same formula, wasn’t as soluble, which rendered it ineffective. Abbott was forced to pull the drug from market until they could reformulate it as a caplet in 1999.
The ordeal cost the company an estimated $250 million (not to mention the tens of thousands of patients who went without essential medication). Disappearing polymorphs cause plenty of legal headaches for drugmakers too. For example, when a Canadian pharmaceutical company wanted to produce Form I of ranitidine (AKA Zantac) after the patent expired, they were sued by the drugmaker Glaxo.
Extract — continue reading at the source.
