title: Water-immiscible room temperature ionic liquids (RTILs) as drug reservoirs for controlled release.
abstract: 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 moll(-1) (BMIM), 0.032 moll(-1) (HMIM) and 0.09 moll(-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.
authors.affiliation: Centre for Drug Delivery Research, The School of Pharmacy, University of London, 29/39 Brunswick Square, London WC1N 1AX, UK.
authors.forename: Vikas
authors.initials: V
authors.lastname: Jaitely
authors.forename: Aysegül
authors.initials: A
authors.lastname: Karatas
authors.forename: Alexander T
authors.initials: AT
authors.lastname: Florence
mesh_terms: D018938:Caco-2 Cells; D002412:Cations; D002470:Cell Survival / Q000187:drug effects; D003692:Delayed-Action Preparations; D003907:Dexamethasone / Q000737:chemistry; D006801:Humans; D007093:Imidazoles / Q000737:chemistry*; D052578:Ionic Liquids / Q000737:chemistry* / Q000633:toxicity; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D012995:Solubility; D013329:Structure-Activity Relationship; D013395:Sucrose / Q000737:chemistry; D013500:Surface Tension; D044366:Transition Temperature; D014783:Viscosity
chemical_list: D002412:Cations; D003692:Delayed-Action Preparations; D007093:Imidazoles; D052578:Ionic Liquids; D004364:Pharmaceutical Preparations; D013395:Sucrose; D003907:Dexamethasone