Discovery of new cocrystals beyond serendipity: lessons learned from successes and failures

Abstract

The past decade has witnessed remarkable progress in cocrystal research, by virtue of the desires to address problematic properties of drugs. Notwithstanding the rapid advancements in knowledge-based cocrystal design, such...

Stoichiometric Diversity of Caffeine and 4-Hydroxybenzoic Acid Cocrystals in Batchelor Vortex Flow

“…16 Interestingly, it has been demonstrated that CAF and 4-HBA cocrystallize in a 1:1 molar ratio, resulting in a mixture of (2:1) and (1:2) cocrystals, 12 which contradicts computational predictions that suggest greater stability for the (1:1) cocrystals. 9,16 However, the formation of CAF/4-HBA (1:1) cocrystals has not yet been achieved. Additionally, it has been revealed that the stoichiometry of the resulting cocrystals is influenced by the initial concentration of the components.…”

“…Consequently, the screening of cocrystals with diverse stoichiometries has garnered considerable attention due to its inherent advantages. − For instance, extensive research on the cocrystallization of caffeine (CAF) with 4-hydroxybenzoic acid (4-HBA) has been conducted using both experimental − and computational methods . Interestingly, it has been demonstrated that CAF and 4-HBA cocrystallize in a 1:1 molar ratio, resulting in a mixture of (2:1) and (1:2) cocrystals, which contradicts computational predictions that suggest greater stability for the (1:1) cocrystals. , However, the formation of CAF/4-HBA (1:1) cocrystals has not yet been achieved. Additionally, it has been revealed that the stoichiometry of the resulting cocrystals is influenced by the initial concentration of the components .…”

“…Cocrystallization has become an essential method within the pharmaceutical industry for the modification of the physicochemical properties of active pharmaceutical ingredients (APIs), such as solubility, dissolution rate, bioavailability, and stability. − The existence of cocrystals in various stoichiometries between the same API and coformer can expand the repertoire of possible solid forms for a given API. Consequently, the screening of cocrystals with diverse stoichiometries has garnered considerable attention due to its inherent advantages. − For instance, extensive research on the cocrystallization of caffeine (CAF) with 4-hydroxybenzoic acid (4-HBA) has been conducted using both experimental − and computational methods . Interestingly, it has been demonstrated that CAF and 4-HBA cocrystallize in a 1:1 molar ratio, resulting in a mixture of (2:1) and (1:2) cocrystals, which contradicts computational predictions that suggest greater stability for the (1:1) cocrystals. , However, the formation of CAF/4-HBA (1:1) cocrystals has not yet been achieved.…”