alt Hacker NewsEvery time I look into those I come away thinking that Occam's Razor would suggest a different explanation: the original characterization was, knowingly or not, incorrect. Patents so frequently fail to contain sufficient information to allow a practitioner skilled to in the appropriate arts to reproduce the claims that it seems more plausible that the disappearing polymorph stories should be reclassified as "someone was caught fibbing" stories. In the replication crisis, we don't assume that the problem is that something about the world has changed, we assume that the original was flawed, and we should do the same here.
It would be much more convincing if there were more cases that weren't economically significant. A strange property of chemistry that only comes up when money and lawyers are involved seems inherently suspicious.
I skimmed the literature on this and the ritonavir story seems legit.
There really is a peer-reviewed paper saying that there are five crystalline forms of the stuff. ("Elucidation of crystal form diversity of the HIV protease inhibitor ritonavir by high-throughput crystallization", Applied Physical Sciences, Feb 2003).
It really does seem that in 1998 the more stable Form II suddenly started coming out of the factory, with lower solubility and such bad oral bioavailability that the oral capsules were withdrawn from the market until Abbott figured out a new way to make the drug. (I think they were already moving from a capsule to a gelcap and the gelcap didn't have the same issue? Just reading … this is not such a good source perhaps but lovely bare HTML: https://www.natap.org/1998/norvirupdate.html )