Physicochemical and Thermodynamic Basis of Dissolution Enhancement of Biopharmaceutics Classification System Class II Drugs in Deep Eutectic Solvents

Deep eutectic solvents (DES) offer a sustainable, tunable platform for overcoming dissolution‐limited oral bioavailability in Biopharmaceutics Classification System (BCS) class II drugs. This review benchmarks DES against established solubility‐enhancement approaches, examines their physicochemical and thermodynamic properties and the interactions governing drug dissolution, and classifies drugs showing improved dissolution across DES systems, correlating molecular structure, DES composition, and solubilization mechanism. Key factors governing solubilization, including hydrogen bond donor (HBA), hydrogen bond acceptor (HBD), their molar ratio, and water content, are discussed. Oral formulation strategies incorporating DES, including eutectogels and liquid formulations, are examined, emphasizing that improved dissolution must be paired with appropriate delivery design. Safety, toxicity, regulatory status, manufacturing scalability, and stability are critically evaluated, highlighting the compositional and system‐dependent nature of DES performance. Overall, this review provides a physicochemically grounded framework for the rational development of sustainable DES platforms for dissolution‐limited drug systems.