Room temperature ionic liquids and their mixtures: potential pharmaceutical solvents

Area of Science:

• Green Chemistry
• Materials Science
• Pharmaceutical Science

Background:

• Room temperature ionic liquids (RTILs) are organic salts liquid at ambient temperatures, recognized for their potential as environmentally friendly solvents.
• RTILs possess unique properties due to their large, asymmetric organic cations and various anions.
• Their tunable nature makes them attractive for diverse chemical applications, including drug formulation.

Purpose of the Study:

• To investigate the solvency of specific alkyl imidazolium salts for poorly water-soluble model drugs, albendazole and danazol.
• To evaluate the potential of these RTILs as pharmaceutical solvents or cosolvents.
• To explore methods for adjusting the aqueous miscibility of RTILs for enhanced pharmaceutical applications.

Main Methods:

• Testing the solubility of albendazole and danazol in alkyl imidazolium salts, specifically 1-butyl-3-methylimidazolium hexafluorophosphate ([bmim]PF(6)).
• Assessing the impact of [bmim]PF(6) on drug solubility, noting a >10,000-fold increase for albendazole.
• Investigating the effect of adding a second, more water-miscible RTIL (e.g., 1-hexyl-3-methylimidazolium bromide, [hmim]Br) to improve the aqueous miscibility of [bmim]PF(6).

Main Results:

• The solubility of albendazole was dramatically increased (>10,000 times) in [bmim]PF(6).
• The aqueous miscibility of poorly water-miscible RTILs like [bmim]PF(6) can be enhanced by incorporating more miscible RTILs.
• The degree of miscibility improvement correlated with the hydrophilicity of the added RTIL.

Conclusions:

• Alkyl imidazolium salts demonstrate significant potential as effective pharmaceutical solvents for poorly water-soluble drugs.
• The ability to tune the aqueous miscibility of RTILs broadens their applicability in pharmaceutical formulations.
• These findings support the use of RTILs as versatile and tunable green solvents in drug development.