Discovering New Co-Crystals

Abstract

A new and systematic method for co-crystal screening has been developed, based on improvements in the understanding of the thermodynamic factors that influence co-crystal formation. This method works from the premise that pure component solubilities determine the concentration regions to screen for new co-crystals, rather than the stoichiometry of the co-crystal. An extended phase diagram screen gives the composition ranges in which the co-crystal is the stable crystalline form. The method is based on the measurement of saturation temperatures which are experimentally easily accessible using standard laboratory equipment. The method has been validated using both carbamazepine and cinnamic acid with a number of co-formers in ethanol solvent. New co-crystals of carbamazepine with isonicotinamide, benzamide and 3-nitrobenzamide, and of cinnamic acid with 3-nitrobenzamide have been discovered.

Pharmaceutical Cocrystals: An Overview

“…A new method was developed for the screening of the cocrystals by measuring the saturation temperature of cocrystals and their components [15] . Saturation solubility of drug and coformer is determined separately at particular temperature known as reference temperature and saturation temperature of the solution is determined by heating with 0.3°/min.…”

“…In literature, researchers have defined the cocrystals in various definitions [13][14][15][16] . The generally accepted definition of cocrystals was proposed by 46 scientists during the Indo-US Bilateral Meeting sponsored by the Indo-US Science and Technology Forum titled "The Evolving Role of Solid State Chemistry in Pharmaceutical Science", which was organized in Delhi, India in 2012.…”

Studies of preparation, characterization, and solubility of mefenamic acid-nicotinamide co-crystal synthesized by using melt crystallization method

“…Co-crystal can be defined as crystalline complexes of two or more neutral molecular constituents bond together in the crystal lattice through noncovalent interaction, primarily hydrogen bond [6]. In crystal engineering, crystals can be viewed as supramolecules consisting of superatoms bound together with intramolecular interactions instead of covalent bonds.…”

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“…Therefore, co-crystallization would be better alternative to replace other solid forms (metastable polymorphs, amorphous form, salts etc.) and thus offer greater stability and other desirable properties suitable for processing 13,14 .…”