Screening for Inclusion Compounds and Systematic Construction of Three‐Component Solids by Liquid‐Assisted Grinding

Abstract

The rational construction of cocrystals (crystalline solids made up of more than one molecular component) has recently attracted the attention of solid-state scientists and materials chemists.[1] The interest, founded on the growing number of applications of multicomponent solids, includes the discovery of new cocrystals, as well as the development of efficient methods for cocrystal synthesis and screening. [2, 3] Whereas reliable strategies have been developed to design and construct two-component (binary) cocrystals by using hydrogen bonds, [4] halogen bonds, [5] p···p [6] or van der Waals forces, [7] the construction of ternary and higher-order cocrystals still presents a challenge.

Indomethacin–Saccharin Cocrystal: Design, Synthesis and Preliminary Pharmaceutical Characterization

“…Interestingly, the addition of minute quantities of ethyl acetate or ethanol or water enhanced the transformation kinetics. This phenomenon of enhanced kinetics has also been observed with other cocrystals (23). Indeed, systematic studies to better understand cocrystal formation kinetics and mechanisms under ambient and subambient temperatures and in the presence of solvents or water are currently undergoing in our laboratory.…”

Dual Mechanoenzymatic Kinetic Resolution of (±)‐Ketorolac

“…Minimization of solvent use is a determinant factor for the fulfillment of the green chemistry principles. In this regard, and in contrast with previous reports of enzymatic resolution of racemic Ketorolac in which the use of solvent is excessive, mechanoenzymatic reactions can be conducted under the liquid‐assisted grinding (LAG) technique, which employs minimal amounts of solvent to carry out chemical transformations in a ball mill. Aiming to increase the enantiomeric excess of the ( S )‐enantiomer of Ketorolac in the present mechanoenzymatic approach several LAG additives (considering that methanol is being used here as a reagent) were evaluated (Table ).…”

An Investigation of the Causes of Cocrystal Dissociation at High Humidity

“…The 1:1 adipic acid cocrystal of caffeine was prepared by liquid‐assisted grinding in the presence of nitromethane. After 10 days at 98% RH, this cocrystal partially dissociated, as evidenced by a weak reflection in the PXRD trace at 10.5° 2 θ corresponding to caffeine monohydrate (Fig.…”