Cyclodextrin-Based Supramolecular Ternary Complexes: Emerging Role of Ternary Agents on Drug Solubility, Stability, and Bioavailability

The aqueous solubility of active drug moiety plays a crucial role in the development of an efficacious formulation. The poor aqueous solubility of BCS class II and IV drugs is manifested as poor bioavailability. Preparation of cyclodextrin inclusion complex to improve the solubility, stability, and bioavailability is a well-established technique. The latest trend in cyclodextrin research is focused on ternary complexes wherein an auxiliary agent such as water-soluble polymers, organic ions, metals, or amino acids is incorporated in the inclusion complex. The cyclodextrin-based supramolecular ternary complex offers significant advantages over binary complex specifically for oral drug delivery. Compared with the binary complex, the ternary complex exhibits better complexation efficiency and stability constant. Moreover, the ternary complex has a major advantage of reducing the concentration of cyclodextrin required to achieve maximum solubility and stability. Lately, in silico molecular modeling has gained tremendous attention as a preliminary tool to evaluate the cyclodextrin-based ternary or binary complex which has been discussed. This review gives an insight into various ternary agents explored worldwide, significant observations, safety, and clinical studies carried out on ternary cyclodextrin complexes.