An industrial perspective on co-crystals: Screening, identification and development of the less utilised solid form in drug discovery and development

Pharmaceutical Crystals: Development, Optimization, Characterization and Biopharmaceutical Aspects

“…On the other hand, the multicomponent crystal systems comprise drug molecules that have different intermolecular interactions with other molecules (guest molecule or coformer) or ion, resulting in the formation of a new solid form without alterations in the covalent chemistry [7,14,15]. This group is formed by solvates, hydrates, co-crystals, salts, and a combination of these (like salt hydrates, salt solvates, co-crystal solvates, co-crystal salt, and co-crystal salt solvates) [14,[16][17][18][19][20].…”

“…In addition, each multi-component system may have polymorphs [21]. The multicomponent systems can modify different properties of the API without changing its molecular structure, resulting in improved solubility, dissolution, and bioavailability, among others benefits [15].…”

“…Co-crystals are formed by a neutral drug molecule and a co-crystal former in stoichiometry relation [15,25]. Both molecules reside in the same crystal lattice and are bonding through non-covalent interactions.…”

“…Both molecules reside in the same crystal lattice and are bonding through non-covalent interactions. In particular, hydrogen bonds are especially important in co-crystals but dipolar, π-stacking, van der Waals and halogen-hydrogen interactions may also stabilize the crystalline structure [6,14,15].…”

“…The "pKa rule" is an accepted method used in the salt formation that uses the difference between pKa values of API and coformer to predict their behavior. The salt formation is possible if ΔpKa (ΔpKa = pKa base -pKa acid ) is less than 3 [15].…”