Hydrophobic hydration of analgesics and diltiazem complexes explored by electrochemical impedance spectroscopy and diffusion-ordered spectroscopy

In the context of drug-drug interactions, the combination of benzodiazepine (BDZ) or benzothiazepine (BTZ) antidepressant/hypnotics with commonly used analgesics, including over-the-counter nonsteroidal anti-inflammatory drugs (NSAIDs), has been reported to decrease the effectiveness of analgesics. This study aimed to analyze the diffusion behavior of analgesics and diltiazem (DTZ), which was used as a structural model of BDZ/BTZ, in solution using NMR diffusion-ordered spectroscopy (DOSY) and electrochemical impedance spectroscopy (EIS). Analgesics and DTZ were dispersed as free entities in deuterated dimethyl sulfoxide (an aprotic solvent), whereas oligomeric clathrates were observed in heavy water (a protic solvent). These findings suggest that the hydrophobic hydration of the complex formed by acidic and basic drugs may involve intermolecular electrostatic interactions embedded within the hydrogen-bonding network in water.