Virtual Cocrystal Screening

Active Pharmaceutical Ingredients (APIs) are bioactive molecules, normally used in the solid form, and employed in medicine. Although APIs can be part of a medicine in amorphous form, the major part of medicines contain APIs in crystalline forms like salts or polymorphs.

The search for new polymorphs and salts involves significant effort and presents a lot of interest. This is because new crystalline forms can improve physicochemical and pharmaceutical properties of a drug, so that the new drugs can be patented and commercialized.

Recently, another kind of solids – cocrystals – have created great expectations because it has been observed that they can improve, through physicochemical changes, the stability and bioavailability of the original drug. These improvements convert cocrystals into an attractive target for the pharmaceutical industry and its future possibilities position them inside the strategy for the development of new drugs.

Our Virtual Cocrystal Screening method is a high-throughput software capable to predict, for a specific API, what coformers are the most suitable candidates for cocrystallization, resulting, unlike the long and expensive conventional screening methods, in time and costs reductions for our partners.

The Virtual Cocrystal Screening software was developed by Professor Christopher Hunter and co-workers at the University of Sheffield and their findings were published in 2011 in the Royal Society of Chemistry’s renowned journal Chemical Science. This technology is based on the principle that the strongest H-bond is formed between the best H-bond donor and the best H-bond acceptor. Thus, when multiple H-bond contacts can be formed between the API and the coformer a hierarchical combination of the best H-bond donors and acceptors is established by the method. This approach assumes that cocrystals only have attractive electrostatic interactions and that the difference between the interaction site pairing energies of the cocrystal and the two pure forms provides a measure of the probability of forming a cocrystal based on the formation of more favourable intermolecular interactions. Furthermore, the software does not require the knowledge of the crystalline structure.

In order to validate it, a blind test has been conducted by us with four APIs. Less than 1% of those coformers from the GRAS list with the highest probability of cocrystallization were tested under standard experimental screening conditions and new cocrystals for three out of four APIs were isolated; this demonstrates the potential of the technology.

The finding of new polymorphs susceptible to be patented is nowadays more difficult. Given this situation, cocrystallization represents a highly probable possibility to improve physicochemical properties of current drugs. The challenge is to be able to process the 2500 cocrystallization possibilities for a single API, and our high-throughput computational virtual screening systems (REG) appears to be the best alternative to achieve it since, in comparison with the traditional experimental screenings, they drastically reduce time and costs.

For those companies wishing to be leaders in cocrystal development and drug discovery, acces to our prediction software represents a real opportunity to be more competitive and an advantage with respect to the competitors.

In CIRCE, as a result of our high principles and since we are a company that offers pharmaceutical services, we are interested in collaborating with our clients in a very active manner, becoming their partners and creating long-term relations. For this reason, we propose global solutions through unique and state of the art technologies, to solve problems related to your APIs as well as developing protection strategies and/or extending the intellectual properties of your New Chemical Entities (NCEs).

You can download our Virtual Cocrystal Screening technical file here.

For further information, please Contact us.