Water-immiscible room temperature ionic liquids (RTILs) as drug reservoirs for controlled release

Water-immiscible room temperature ionic liquids (RTILs) have a largely unexplored potential as pharmaceutical solvents and reservoirs. This paper explores some relevant properties of the hexafluorophosphate (PF6−) salts of butyl, hexyl and octyl-3-methylimidazolium cations (BMIM, HMIM, OMIM, respectively). The dodecyl analogue is solid at room temperature, but its melting point can be lowered by addition of the lower homologues. Although water-immiscible, the liquids absorb water to an extent depending on their structure, the higher alkyl analogues having a lower affinity for absorbed water. The RTIL/water partition coefficients of sucrose, penicillin V potassium, dexametasone, progesterone and dehydro-epiandrosterone have been compared with octanol–water coefficients. The viscosities of the salts were measured in anhydrous, water-saturated and intermediate states. The PF6− ionic liquids display a low and decreasing aqueous solubility as the alkyl chain length is increased: 0.035 mol l−1 (BMIM), 0.032 mol l−1 (HMIM) and 0.09 mol l−1 (OMIM). The release of sucrose and dexametasone from RTIL reservoirs into water can be prolonged over 48 h. Saturated solutions of these RTILs show little toxicity towards Caco-2 cells, although the OMIM derivative, which is more surface-active, has a small effect on cell viability.