Cosolvency and cosolvent polarity

Area of Science:

• Physical Chemistry
• Pharmaceutical Sciences
• Drug Delivery

Background:

• Poorly soluble drugs present formulation challenges.
• The log-linear solubility equation approximates drug solubility in cosolvent-water mixtures.
• Understanding cosolvent properties is key to enhancing drug solubility.

Purpose of the Study:

• To correlate cosolvent polarity indexes with the slope (sigma) of the log-linear solubility equation.
• To identify physicochemical parameters that best predict drug solubility.
• To establish a basis for estimating cosolvent requirements for nonpolar drugs.

Main Methods:

• Examined solubilities of phenytoin, benzocaine, and diazepam in cosolvent-water mixtures.
• Related solubility plot slopes (sigma) to cosolvent polarity indexes (dielectric constant, solubility parameter, surface tension, interfacial tension, octanol-water partition coefficient).
• Assessed hydrogen bonding capacity (HBD, HBA) and its correlation with sigma.

Main Results:

• Cosolvent polarity indexes reflecting cohesive properties (solubility parameter, interfacial tension) showed high correlation with sigma.
• Hydrogen bonding ability (HBD, HBA) also highly correlated with sigma.
• Theories involving solubility parameters and interfacial tension improved correlation accuracy.

Conclusions:

• Physicochemical properties of cosolvents, particularly cohesive and hydrogen bonding characteristics, are crucial for predicting drug solubility.
• The study provides a framework for estimating cosolvent type and quantity for solubilizing nonpolar drugs.
• This research aids in optimizing pharmaceutical formulations for poorly soluble compounds.