Influence of functional groups on drug solubility using choline chloride-based deep eutectic solvents

Area of Science:

• Computational Chemistry
• Pharmaceutical Sciences
• Materials Science

Background:

• Drug solubilization remains a critical challenge in pharmaceutical research, hindering the development of effective therapeutics.
• Deep eutectic solvents (DES), formed from hydrogen bond acceptors (HBA) like choline chloride (ChCl) and various hydrogen bond donors (HBDs), offer a novel approach to address poor drug solubility.
• Understanding the molecular interactions between DES components and drug molecules is crucial for optimizing solubility.

Purpose of the Study:

• To investigate the sigma-surface, sigma-profile, and sigma potential of 35 water-insoluble drugs using DES.
• To explore the impact of hydrogen bond donors and acceptors on drug solubility at a molecular level.
• To identify promising DES formulations for enhancing the solubility of poorly soluble drugs.

Main Methods:

• Utilized COSMOthermX and TURBOMOLE for data processing and COSMO simulations to evaluate solvation effects.
• Performed geometry optimizations using density functional theory (DFT) with the BP86 functional and TZVP basis set.
• Generated COSMO files using the BP_TZVP_19.ctd parameterization in COSMOthermX.

Main Results:

• Choline chloride (ChCl) demonstrated enhanced interaction with drugs containing donor groups like carboxyl (-COOH), amino (-NH₂), and hydroxyl (-OH) due to strong hydrogen-bonding capabilities.
• The presence of HBDs and HBAs in drugs significantly influences their solubility in DES.
• Acid, alcohol, and amide-based DES formulations showed potential as carriers for poorly soluble drugs.

Conclusions:

• Acid, alcohol, and amide-based DESs are identified as potential carriers for improving the solubility of poorly soluble drugs.
• The study highlights the necessity of understanding the physiochemical characteristics of DES for maximizing drug solubility.
• Molecular-level insights into drug-DES interactions are key to developing effective drug delivery systems.