Biopharmaceutics Classification System (BCS) Class II and IV drugs suffer from poor aqueous solubility and hence low bioavailability. Most of these drugs are hydrophobic and cannot be developed into a pharmaceutical formulation due to their poor aqueous solubility. One of the ways to enhance the aqueous solubility of poorlywater-soluble drugs is to use the principles of crystal engineering to formulate cocrystals of these molecules with water-soluble molecules (which are generally called coformers). Many researchers have shown that the cocrystals significantly enhance the aqueous solubility of poorly water-soluble drugs. In this review, we present a consolidated account of reports available in the literature related to the cocrystallization of poorly water-soluble drugs. The current practice to formulate new drug cocrystals with enhanced solubility involves a lot of empiricism. Therefore, in this work, attempts have been made to understand a general framework involved in successful (and unsuccessful) cocrystallization events which can yield different solid forms such as cocrystals, cocrystal polymorphs, cocrystal hydrates/solvates, salts, coamorphous solids, eutectics and solid solutions. The rationale behind screening suitable coformers for cocrystallization has been explained based on the rules of five i.e., hydrogen bonding, halogen bonding (and in general non-covalent bonding), length of carbon chain, molecular recognition points and coformer aqueous solubility. Different techniques to screen coformers for effective cocrystallization and methods to synthesize cocrystals have been discussed. Recent advances in technologies for continuous and solvent-free production of cocrystals have also been discussed. Furthermore, mechanisms involved in solubilization of these solid forms and the parameters influencing dissolution and stability of specific solid forms have been discussed. Overall, this review provides a consolidated account of the rationale for design of cocrystals, past efforts, recent developments and future perspectives for cocrystallization research which will be extremely useful for researchers working in pharmaceutical formulation development.

Precipitation of curcumin, a poorly water-soluble drug, has been carried out by the liquid antisolvent technique in the presence of ultrasound and stabilizers. Curcumin particles with varied morphology were observed to have formed during precipitation in the presence of ultrasound and additives such as sodium dodecyl sulfate (SDS), Tween 80, hydroxyl propyl methylcellulose (HPMC), polyvinyl pyrrolidone (PVP), and bovine serum albumin (BSA). Characterization of the precipitated particles reveals that curcumin particles precipitated with ultrasound and large polymeric stabilizers such as HPMC, PVP, and BSA are superstructures formed by aggregation of several primary curcumin nanoparticles. The particles in these cases appeared to be loose aggregates (of ~1–5 μm in size) composed of several curcumin nanoparticles (~50–200 nm in size). On the other hand, curcumin particles precipitated in the presence of ultrasound and without additive as well as small-molecule stabilizers like SDS and Tween 80 appear more fused (the primary building blocks of these particles were not clearly visible). Moreover, curcumin particles precipitated in the presence of ultrasound only and particles precipitated in the presence of ultrasound along with additives were found to exist in the orthorhombic form, whereas raw curcumin and curcumin particles precipitated without any additive and without ultrasound were found to exist in the monoclinic form. The results obtained in this work suggest that curcumin particles with the desired physical form and morphology can be engineered through a careful manipulation/choice of ultrasound and additives during precipitation.