Crystal Engineering for Innovations in Medicine - Canada Excellence Research Chair in Crystal Engineering for Green Chemistry and Sustainable Materials

We aim to apply Crystal Engineering to the design, synthesis, and application of innovative approaches to medicine. Our focus is on the development of (i) pharmaceutical cocrystals and (ii) cyclobutanes generated in crystals as small-molecule drugs and platforms for theranostics. We seek to define green approaches to medicine by using mechanochemistry to form cocrystals and/or to carry out solid-state reactions to generate CBs as active pharmaceutical ingredients (APIs). This research is conducted with faculty in the Pharmacology Institute of Sherbrooke (IPS) and the Centre d’Imagerie Moléculaire de Sherbrooke (CIMS). A large majority of marketed pharmaceutical products are solids, with on the order of 90% of those products (e.g. tablets) with the API being in a crystalline form. The pharmaceutical industry itself is also the largest consumer of organic solvents among chemical manufacturing industries and the highest waste generator. Therefore, the introduction of green chemistry approached to the pharmaceutical industry is an area of great interest.

The chemical structure and crystal structure of Entresto — Structural formula and X-Ray crystal structure of Entresto. The sodium ions are represented as polyhedral in the presented crystal structure and the uncoordinated water molecules have been removed. The atomic coordinates of the crystal structure were retrieved from the Cambridge Structural Database, REFCODE: NAQLAU. Crystal structure image generated with VESTA (J. Appl. Cryst. 2011, 44, 1272-1276)

Pharmaceutical cocrystals have gained increasing importance during the last decade. The solids possess one component as an API and a partner component as either a second API (i.e. drug-drug cocrystal) or GRAS molecule (Generally Recognized as Safe by the US-FDA). Cocrystals make available opportunities to create novel multidrug combinations as a single crystalline phase and improve properties (e.g. bioavailability, stability).

The FDA also recently re-classified pharmaceutical cocrystals as ‘drug substances’, which now affords opportunities for intellectual property (IP) protection for any newly formed pharmaceutical cocrystals. Some notable examples of pharmaceutical cocrystals include Entresto, and Seglentis. Entresto is a cocrystal composed of sacubitril and valsartan for treatment of chronic heart failure, which was approved in 2015. Seglentis, a drug-drug cocrystal of tramadol hydrochloride and celecoxib, was approved in 2021 for acute pain relief. Pharmaceutical cocrystals also enable green pathways to improved medicines since needs to create new classes APIs can be bypassed and, in doing so, circumvent waste generation. The use of mechanochemistry (e.g. solvent-free grinding) to form pharmaceutical cocrystals also minimizes needs for solvent for crystallization.

Our group aims synthesize cyclobutanes in the solid state for new applications as theranostics for prostate health. Theranostics involve combining therapeutic and diagnostic techniques with a suitable pharmaceutical agent. A radioactive drug with a pharmaceutical platform identifies the presence of cancerous prostate cells by imaging (e.g. PET scanning). The same platform is then used with a second radioactive drug to deliver aptly dosed therapy to treat the main and metastatic tumors.