Chemistry and Modern Techniques of Characterization of Co-Crystals

Abstract

Co-crystals are multicomponent molecular materials held together through non-covalent interactions that have recently attracted the attention of supramolecular scientists. They are the monophasic homogeneous materials where a naturally occurring pharmaceutical active ingredient (API) and a pharmaceutically acceptable co-crystal former are bonded together in a 1:1 via non-covalent forces such as H-bonds, π–π, and van der Waals forces. Co-crystallization is a promising research field, especially for the pharmaceutical industry, due to the enormous potential of improved solubility and bioavailability. Co-crystals are not the only multicomponent molecular materials, as there are many other forms of multicomponent molecular solids such as salts, hydrates, solvates, and eutectics. The formation of co-crystals can roughly be predicted by the value of ∆pKa, that is, if the ∆pKa is more than 3, then this monophasic homogeneous material usually falls in the category of salts, whereas if the ∆pKa is less than 2, then co-crystals are usually observed. A number of methods are available for the co-crystal formation, broadly classified into two classes established on state of formation, that is, solution-based and solid-based co-crystal formation. Similarly, a number of techniques are available for the characterization of co-crystals such as Fourier transforms-infrared spectroscopy, single-crystal and powder X-ray diffraction, etc. In this chapter, we will discuss the available methods for co-crystallization and its characterization.

Preparation, Crystal Structure, Supramolecular Assembly, and DFT Studies of Two Organic Salts Bearing Pyridine and Pyrimidine

“…The combinations of various compounds such as sulfalene-pyrimethamine, sulfamethoxazole-trimethoprim, and sulfadoxine-pyrimethamine have also lost their effectiveness against malaria due to the same reason . Among various synthetic approaches for rapid modification of the existing drugs, co-crystallization procedure is found to be an efficient protocol to obtain new drug combinations with high potential against various harmful parasites. , Co-crystallization could enhance the physical properties like solubility and stability, as can be seen in the case of the increased hydration stability of the co-crystals of isoniazid with 5-fluorocytosine . The isoniazid-entacapone co-crystal system was found to have improved permeability, solubility, and diffusion .…”

Alternating [ML2(MeOH)2] and [ML2(EtOH)2] layers in low-temperature ferromagnets [ML2(MeOH)2][ML2(EtOH)2] (M = CoII, NiII or CoII0.5NiII0.5)

“…43 Similar dimer formation is often observed in co-crystals where two or more components form a single crystal structure without proton transfer. 44,45 Co-crystals can be used to modulate physical properties such as the melting point, solubility, dissolution rate, stability or crystallinity of the original molecules. 46,47 In…”