ABSTRACT
Different deep eutectic systems (DES) of choline chloride (CC)-urea (UA) (1:2), CC-glycerol (GLY) (1:2), CC-malonic acid (MA) (1:1), and CC-ascorbic acid (AA) (2:1) were generated and characterized by polarized light microscope (PLM) and Fourier transform infrared spectroscope (FTIR). The equilibrium solubility of celecoxib (CLX) in DES was compared to that in deionized water. The CC-MA (1:1) system provided ~10,000 times improvement in the solubility of CLX (13,114.75 µg/g) and was used for the generation of the CLX-DES system. The latter was characterized by PLM and FTIR to study the microstructure and intermolecular interaction between the CLX and CC-MA (1:1) DES. FTIR demonstrated the retention of the chemical structure of CLX. In vitro drug release studies in FaSSIF initially demonstrated high supersaturation, which decreased by ~2 fold after 2 h. Density functional theory (DFT)-based calculations provided a molecular-level understanding of enhanced solubility. Gibbs free energy calculations established the role of the strongest binding of CLX with CC and MA. A phase solubility study highlighted the role of hydrotropy-induced solubilization of the CLX-DES system. Animal pharmacokinetic studies established 2.76 times improvement in Cmax, 1.52 times reduction in tmax, and 1.81 times improvement in AUC0-∞. The overall results demonstrated the potential of developing a DES-based supersaturating drug-delivery system for pharmaceutical loading of drugs having solubility and dissolution rate-limited oral bioavailability.
ABSTRACT
The deep eutectic system (DES) is a relatively new concept in the field of drug delivery science. DES is a class of eutectic mixtures comprised of two or more components, with a eutectic point far below than the melting temperature of the pure components. The strong hydrogen bonding interactions between DES constituents are responsible for significant lowering of melting point in DES. A significant number of molecules cannot reach from drug discovery phase to drug development phase because of poor biopharmaceutical attributes, such as solubility and permeability. DES can be a novel alternative to overcome these issues. In last few years DESs have been widely used in different pharmaceutical and chemical processes. However, comprehensive information regarding their drug delivery potential is not available. This review deals with fundamental aspects such as types, preparation, thermodynamics, toxicity, biodegradability and their applications in the field of drug delivery. Current challenges, future prospects and translational aspects of DES as drug delivery system have also been discussed.
