Be Prepared for Scale Up of Co-crystal Production

Dr. Vaibhav Sihorkar, Head of Pharmaceutical Development at Aurigene Discovery Technologies in India, gave Pharma IQ his insights on existing challenges to co-crystal commercialisation.

What is the major challenge in achieving scale up of co-crystal production?

I foresee the issue of co-crystal scale up, as the lack of knowledge about the concept itself. The thermodynamics of co-crystal formation are not well understood at times, hence arbitrarily synthesising co-crystal by trial and error method has become quite a norm across scientific fraternity, except for a few distinguished groups. The focus is more on the characterisation part, and I can see scientists getting overawed by tools like SXRD and SS-NMR to prove that they have characterised the co-crystal. The job starts from there, if this concept has to go further.

The first and foremost thing is to have clarity in scientific fraternity. To know when and how a compound will form a co-crystal. This should not be just a random trial and error check. It goes beyond saying that most of the researchers are engaged in just doing some synthetic work, and analyse the solid recovered using tools like SXRD to claim that they have found co-crystal. Unless understanding the design of a co-crystal, goes beyond a handful of research labs, I do not foresee this concept getting successfully in the armamentarium from commercial sense.

There are also other issues to consider in co-crystal production, like solid phase purity, amorphous impurity of co-crystal, polymorph of co-crystal, hydrate/solvates of co-crystals. Moreover, robust and scalable methods of scale up need to be established.

The next challenging task is to ensure that these co-crystals withstand the processes encountered en route and during drug development. In parallel to this, you need to convince  management and the organisation that the concept of co-crystals offers you something substantial, much more than that could be achieved by some enabling excipients to address stability or solubility issues.

You need to be ready to address regulatory questions, as this a multi-component system and you may also need to satisfy that both exist as co-crystal during the API scale up, product development and shelf stability of the API and drug product.

This is something achievable, but we have still not crossed the first hurdle as of yet. With the mad rush of exploiting such concepts to create an IP space for an existing API, we may really miss a structured approach in near foreseeable future.