**2. Techniques of co-crystallization**

Various methods for co-crystal formation are currently employed, which may be broadly categorized into two classes established on the state of formation:

#### *Chemistry and Modern Techniques of Characterization of Co-Crystals DOI: http://dx.doi.org/10.5772/intechopen.108694*

solution-based and solid-based methods [7]. The solution-based techniques utilize large amounts of solvents, which require the separation of solvents after crystallization; on the other hand, solid-based route requires no or limited amount of a solvent [8]. The solution co-crystallization has several advantages over solid-state processes comprising better regulation of crystal properties, higher purity, and greater industrial scale. Solution co-crystallization can completely remove impurities from the crystallized product, helping to restrain challenges to achieve selective polymorphic crystallization. It is also a useful strategy for manufacturing co-crystals on an industrial level as the tools essential for extensive fabrication have been previously widely used in the pharmaceutical, food, and agrochemical manufacturing units. Solution co-crystallization has potential applications in various steps of co-crystal production, from initial screening to scale-up for commercial fabrication [9]. Though the solution co-crystallization is beneficial, solid-state co-crystallization is important from the green chemistry perspective.

## **2.1 Solution-based co-crystallization of nutraceuticals**

Nutraceuticals which are a novel category of mixtures with recognized best-ever protection that can be used as attainable contenders are naturally arising for crystallization in the pharmaceutical industry. In 1989, Nutraceuticals, a terminology devised by DeFelice could be demarcated as a diet (or portion of a diet) that offers health or medical assistance, containing the preclusion or cure of a syndrome. Common types of nutraceuticals comprise polyphenols (e.g., phenolic acids, coumarins, stilbenes, and flavonoids) and vitamins [10]. There exist well-recognized approaches for the preparation of co-crystals, which result in crystals with desirable properties that help to evaluate crystal habit and other characteristics [11]. Isothermal ternary phase diagrams (**Figure 2**) show co-crystallization stability area when different components of the co-crystal are dissolved in solvents having similar and dissimilar solubility [12].
