Cocrystal
[2][3] Cocrystals can encompass many types of compounds, including hydrates, solvates and clathrates, which represent the basic principle of host–guest chemistry.
Knowledge of the intermolecular interactions and their effects on crystal packing allowed for the engineering of cocrystals with desired physical and chemical properties.
They have found use in a number of industries, including pharmaceutical, textile, paper, chemical processing, photographic, propellant, and electronic.
These interactions lead to a cocrystal lattice energy that is generally more stable than the crystal structures of the individual components.
Some cocrystals have been observed to exist as polymorphs, which may display different physical properties depending on the form of the crystal.
This approach has been successful with molecules of complementary hydrogen bonding properties, in which case cocrystallization is likely to be thermodynamically favored.
The use of a hydrate or an amorphous phase as an intermediate during synthesis in a solid-state route has proven successful in forming a cocrystal.
As always, a clear connection between pairwise components of the cocrystal is needed in addition to the thermodynamic requirements in order to form these compounds.
Thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) are two commonly used methods in order to determine melting points, phase transitions, and enthalpic factors which can be compared to each individual cocrystal former.
Of these, the most widely studied and used application is in drug development and more specifically, the formation, design, and implementation of active pharmaceutical ingredients (API).
[11] The engineering of cocrystals takes advantage of the specific properties of each component to make the most favorable conditions for solubility that could ultimately enhance the bioavailability of the drug.
Structure-based virtual screening methods, such as docking, makes use of cocrystal structures of known proteins or receptors to elucidate new ligand-receptor binding conformations.
[11] The objective for pharmaceutical cocrystals is to have properties that differ from that expected of the pure APIs without making and/or breaking covalent bonds.
It is thus important in the field of pharmaceuticals to screen for every polymorphic form of a cocrystal before it is considered as a realistic improvement to the existing API.
[11] It is with reasoning that the physical properties of pharmaceutical cocrystals could then ultimately change with varying amounts and concentrations of the individual components.
[6] Even more important for pharmaceutical applications is the ability to alter the stability to hydration and bioavailability of the API with cocrystal formation, which has huge implications on drug development.
[12] A screening procedure has been developed to help determine the formation of cocrystals from two components and the ability to improve the properties of the pure API.
Finally, phase diagram screening and powder X-ray diffraction (PXRD) are further investigated to optimize conditions for cocrystallization of the components.
[6] This procedure is still done to discover cocrystals of pharmaceutical interest including simple APIs, such as carbamazepine (CBZ), a common treatment for epilepsy, trigeminal neuralgia, and bipolar disorder.
CBZ has only one primary functional group involved in hydrogen bonding, which simplifies the possibilities of cocrystal formation that can greatly improve its low dissolution bioavailability.
[11] Another example of an API being studied would be that of Piracetam, or (2-oxo-1-pyrrolidinyl)acetamide, which is used to stimulate the central nervous system and thus, enhance learning and memory.
[6][11] On August 16, 2016, the US food and drug administration (FDA) published a draft guidance Regulatory Classification of Pharmaceutical Co-Crystals.
In this guide, the FDA suggests treating co-crystals as polymorphs, as long as proof is presented to rule out the existence of ionic bonds.
