**1. Introduction**

Nature is the ultimate chemist; it houses a vast repertoire of medicinal molecules. Most of the works done by early physicians are based on the principle of *Medicatrix naturae* or the healing power of nature. With the advent of modern research, the scientific fraternity have perfected the means to isolate nutraceutical APIs (active pharmaceutical ingredients) from plants, animals, and even microbial species. The period between 1981 and 2014, can be claimed as the most promising era of nutraceutical drug discovery. During this time major portion of small molecule ligands to gain USFDA (US Food and Drug Administration) approval were of natural origin. Even

against the COVID-19 pandemic the most potent arsenal interred was a nutraceutical obtained from the blue blood of a horseshoe crab. Time and again it has been proven that, despite having made significant strides in synthetic medicine, nutraceuticals still dominate the healthcare market [1]. Patients for most part prefer non-toxic natural alternatives to synthetic drugs. The origin of nearly half of all human pharmaceuticals can be traced back to natural sources [2].

Widely used OTC (over the counter) aspirin is a popular analgesic obtained from bark of willow tree, vincristine and vinblastine are potent anticancer agents isolated from rosy periwinkle [3], aggrastat a highly recommended anticoagulant is extracted from an afrotropic native the saw-scaled viper [4], these are some of the popular examples of drugs culminated from the nature's repertoire. Nevertheless, despite holding cure to the most intractable of human maladies [5], a very low percentage of marketed medicine is formulated using nutraceutical pharmacophores [6].

Poor absorption from the GI (gastrointestinal) tract and the consequent limitation in systemic bioavailability are predominant roadblocks in pharmaceutical use of nutraceuticals. A fact that is also supported by restrictive solubility profile of nutraceutical molecules. Irrespective of its source of origin, the major contributors of unsuccessful pharmaceutical formulations, are diminished gastro-intestinal (GI) absorption and less than the required systemic bioavailability [7]. The definition of bioavailability defines the fraction of dose following administration that reaches the systemic circulation. It is also a representation of the bio-efficacy or in other words the therapeutic utility of any medicinal compounds [8]. Factors responsible for low bioavailability include molecular instability, poor aqueous solubility and pitiable rate of dissolution and absorption in systemic physiology. Therefore, for exploiting the efficacy of nutraceuticals in active pharmaceutical use, we must concentrate on improving their GI absorption and bioavailability [9]. Several strategies targeting to improve, GI absorption and bioavailability of the therapeutic lead have although been developed, drug modification via co-crystallization is presently the rage of the hour. Like co-crystals of synthetic molecules, nutraceutical co-crystals are crystalline solid composed of a nutraceutical API and a pharmaceutically acceptable excipient also known as the co-former non-covalently bonded in a stoichiometric ratio [10].

The cardinal imperative of the current chapter is to provide an overview of the concept of co-crystallization in modulating the absorption and bioavailability of nutraceutical ligands. Since the ascendency of crystal engineering, co-crystallization has proven to be of immense use in modifying the physicochemical attributes of APIs. The principal advantage of employing co-crystallization strategies is that co-crystals improve the solubility and absorption characteristics of the target API without alternating in any way the intrinsic pharmacological activity of the molecule. In subsequent sections of the current chapter a lot of interesting insights can be gained regarding the properties, strategies, advancement and prospects of co-crystallization in accentuating the use of nutraceuticals in pharmaceutical drug designing.
