A co-crystal is a multi-component crystal containing two or more molecules, Ireland’s University of Limerick’s Mike Zaworotko told delegates at the BioPharma Ambition Conference last month.
The structure is typically composed of an active pharmaceutical ingredient (API) and an excipient, which in theory can be modified to enhance drug processability, stability or bioavailability.
“The goal is to control the structure,” said Zaworotko, adding, “we’re not stuck with what nature gave us in the single component crystal, we can design crystal structures and sometimes improve properties.”
According to Zaworotko, using co-crystals is a low-cost and high-reward route to new and better medicines.
The structures are also low-risk, he added: “Because we can take old molecules, and make them work better.”
While co-crystals are not new, the University’s Bernal Chair of Crystal Engineering and Science Foundation of Ireland research professor said to date, they have been “definitely understudied.”
However Zaworotko said he is observing renewed interest in co-crystals by design.
In the past three years, the US Food and Drug Administration (FDA) has approved three co-crystals, such as Novartis’ Entresto (sacubitril/valsartan) – indicated for heart failure with reduced ejection fraction (HFrEF).
“Entresto is the most interesting. There are two APIs in the co-crystal, which work more efficaciously than if they were delivered separately in a combination drug product.”
The FDA further demonstrated its support of pharmaceutical co-crystals in February, when it released a final guidance detailing changes to the regulatory classification of co-crystals, from intermediate to API.
The guidance responds to industry’s request to clarify the appropriate classification of co-crystals, and consequently reduce current good manufacturing practice (cGMP) burden.
“The FDA has basically fully endorsed co-crystals as drug substances,” said Zaworotko.
But Europe is more hesitant, he said: “They are quite concerned that there could be synergistic or antagonistic effects that need to be addressed before approval.”