Sugar-Based Eutectic Systems Combined with Cyclodextrins for Enhanced Solubility of Carvedilol

(1) Background: Carvedilol is a poorly water-soluble drug, which limits its therapeutic performance. Deep eutectic solvents (DES) and cyclodextrins (CD) are emerging solubilizing agents that can improve drug bioavailability. (2) Methods: Twenty-one DES were prepared using choline chloride and polyols or sugars (xylitol, sorbitol, glucose, and fructose) at different molar ratios with water. α and β cyclodextrins (CD) were added (0.5–2 mM) using two incorporation strategies: (Method 1) addition to the aqueous phase before DES formation; (Method 2) direct addition to the preformed DES. (3) Results: Carvedilol solubility markedly increased with DES–CD combinations. In Method 1, xylitol-based DES provided up to a 16-fold enhancement, especially with β-CD at low concentrations, while glucose and sorbitol systems showed modest effects. Fructose-based mixtures improved mainly at a 2:1:35 ratio without CDs. In Method 2, α-CD with xylitol or sorbitol yielded the highest increases (up to 38.9-fold). (4) Conclusions: The solubilization efficiency depends on DES composition, CD type, and concentration. α-CD combined with xylitol-based DES showed the best results, highlighting this approach as a promising strategy to enhance carvedilol solubility for pharmaceutical applications.