The ritonavir story is super-interesting. It's also interesting how the problem got worked around. Initially, ritonavir had to be shipped as a frozen gel, to slow down the conversion. But this was not optimal at all.
The ultimate solution was hot extrusion: molten ritonavir is dispersed in an inert carrier, and then left to cool. The carrier insulates the droplets from outside contact, so it can't get contaminated with the more stable polymorph.
This idea itself is completely obvious. But like pretty much everything in engineering, it took a decade to perfect the process.
If you have a misfortune to get prescribed Paxlovid for COVID, break a tablet and look at it in a microscope. You'll clearly see the ritonavir droplets embedded inside the carrier material. It's super-cool.
(Ritonavir is used in Paxlovid not because of its antiviral properties, but because it inhibits some liver enzymes, thus slowing down the metabolism of the active ingredient)
The ultimate solution was hot extrusion: molten ritonavir is dispersed in an inert carrier, and then left to cool. The carrier insulates the droplets from outside contact, so it can't get contaminated with the more stable polymorph.
This idea itself is completely obvious. But like pretty much everything in engineering, it took a decade to perfect the process.
If you have a misfortune to get prescribed Paxlovid for COVID, break a tablet and look at it in a microscope. You'll clearly see the ritonavir droplets embedded inside the carrier material. It's super-cool.
(Ritonavir is used in Paxlovid not because of its antiviral properties, but because it inhibits some liver enzymes, thus slowing down the metabolism of the active ingredient)