Inclusion and Non-Inclusion Complexes between Curcumin and β-Cyclodextrin with High-Curcumin Loading and Enhanced Aqueous Solubility Obtained by Mechanochemistry

In this study, we employ mechanochemistry as an innovative strategy, using a Planetary Mill, to obtain supramolecular structures in the solid state between Curcumin (Cur) and beta-cyclodextrin (beta CD), exploring different parameters such as jars and balls material (stainless steel versus zirconium oxide), milling time, as well as the effect on imposing different Cur:beta CD molar ratios. Our findings demonstrate that regardless of the milling material used, the same supramolecular interactions between Cur and beta CD seem to be promoted. However, depending on the molar ratio, different supramolecular modes are produced resulting in inclusion complexes (ICs) or non-inclusion complexes (non-ICs) by a partial or total amorphization of both Cur and beta CD. Independently of the type of supramolecular complex obtained (ICs/or non-ICs), high content of Cur was quantified in all the systems, achieving a Cur content of up to 342 mg per mmol of beta CD, along with an enhancement in Cur aqueous solubility. The Cur:beta CD 1 : 2 complex showed the highest aqueous solubility (around 10-times more soluble than milled Cur). In our conditions, the optimum time to form the supramolecular complexes was 60 min. The stability of the complexes was directly related to the extent of encapsulation of Cur inside the beta CD cavity. Mechanochemistry is a powerful strategy to promote novel supramolecular interactions in the solid state in a rapid, efficient, and environmentally friendly way, which results in the enhancement of physicochemical properties as the aqueous solubility and stability of hydrophobic molecules as the curcumin, allowing their application in the pharmaceutical field.image