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

Abstract

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 β‐cyclodextrin (βCD), 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:βCD molar ratios. Our findings demonstrate that regardless of the milling material used, the same supramolecular interactions between Cur and βCD 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 βCD. 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 βCD, along with an enhancement in Cur aqueous solubility. The Cur:βCD 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 βCD cavity.