Investigation of Carbohydrates and Their Derivatives as Crystallization Modifiers

From Physical Mixtures to Co-Crystals: How the Coformers Can Modify Solubility and Biological Activity of Carbamazepine

“…In this context, the co-crystallization approach appears promising to achieve the crystal engineering of pharmaceutical solids . Generally speaking, a co-crystal can be defined as a crystalline complex of two or more molecules, usually present in a stoichiometric ratio. , Pharmaceutical co-crystals are obtained by combining a pharmaceutical active ingredient (API) with pharmaceutically acceptable molecules, assembled through intermolecular interactions. , The latter are generally different from those found in the crystals of the pure components; consequently, these new crystalline forms exhibit specific physical properties, retaining at the same time the unaltered chemical structure of the APIs. Indeed, it is currently believed that the co-crystallization strategy should not induce changes in the native APIs’ pharmacological profile. − Pharmaceutical co-crystals can show higher solubility and dissolution rate compared to parent crystalline pure phases, with consequent improvement of the bioavailability of APIs even if the latter is not a systematic phenomenon .…”

“…4 Generally speaking, a co-crystal can be defined as a crystalline complex of two or more molecules, usually present in a stoichiometric ratio. 5,6 Pharmaceutical co-crystals are obtained by combining a pharmaceutical active ingredient (API) with pharmaceutically acceptable molecules, assembled through intermolecular interactions. 7,8 The latter are generally different from those found in the crystals of the pure components; consequently, these new crystalline forms exhibit specific physical properties, retaining at the same time the unaltered chemical structure of the APIs.…”

Can pharmaceutical co-crystals provide an opportunity to modify the biological properties of drugs?

“…The term 'co-crystal' originates from 'a composite crystal' and is still a subject of topical debate. There are numerous definitions [6], two of which summarize the main points of view: (i) co-crystals are multicomponent systems where two or more compounds are present, generally in a stoichiometric ratio, both in an ionic or neutral form [7,8]; and (ii) co-crystals are homogeneous crystalline solids containing stoichiometric amounts of discrete neutral molecular species that are solids under ambient conditions (all solids containing ions, including complex transition-metal ions, are excluded) [9]. According to the second definition, ions as co-crystal components are excluded.…”

“…According to the second definition, ions as co-crystal components are excluded. The dividing line between salts and co-crystals can be distinguished by the location of the proton between an acid and a base, taking into account that salt formation requires a difference of almost 3 pKa units between acid-base conjugates [6].…”

“…Combining an API with a pharmaceutically acceptable agent has become an increasingly attractive route for developing new pharmaceutical products with enhanced physicochemical properties. Indeed, cocrystallization with pharmaceutical excipients does not appear to affect the pharmacological activity of an API, but can improve its physical properties, such as solubility, dissolution rate, permeability, stability, and compaction behavior [5,6,12]; in fact, in co-crystals, the molecular components are held together essentially via 'nonbinding' interactions (H-bonds, van der Waals forces, hydrophobic A c c e p t e d M a n u s c r i p t interactions, etc.) without altering the covalent bond structure of the APIs [13], thus retaining their safety and therapeutic properties.…”