Current-stimulated release of solutes solubilized in water-immiscible room temperature ionic liquids (RTILs).

Room temperature ionic liquids (RTILs), salts which are liquid at room temperature, may be water-soluble or water immiscible, depending on the combination of cation and anion. They are efficient solvents for a wide range of solutes including drugs. The water-immiscible RTILs studied in this paper (the 1-butyl, hexyl and octyl 3-methyl imidazolium (BMIM, HMIM, and OMIM) hexafluorophosphate (PF(6)(-)) salts) can act as drug reservoirs. Passage of an electric current through these immiscible liquids can enhance the release of some solutes into an aqueous medium. Current flow (over the range 1-5 mA) increased the release rate of a solubilized hydrophilic solute, (3)H-sucrose, and of a model hydrophobic drug, (3)H-dexametasone. A threefold increase in the release rate of both sucrose and dexamethasone into water was observed under some conditions although the effect of application of current was not always linear. OMIM[PF(6)] was the most responsive liquid. Some measurable physical properties of the ionic liquids change on the application of current. For example, the surface tension of the three RTILs studied decreased significantly on application of current for 15 min (from 47.8 mNm(-1) to 36.2 mNm(-1) for BMIM) but the effect on the surface tension of the OMIM salt was small. Only a small decrease in the viscosity of RTILs was observed. Although the mechanisms of the enhanced release are not yet elucidated, RTILs are potentially interesting depots for electrically controlled drug delivery.

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 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.

Novel anhydrous emulsions: formulation as controlled release vehicles.

Novel anhydrous emulsions, which may offer some advantages as depot or reservoir vehicles for lipophilic drugs in controlled delivery systems, were formulated using castor oil as the disperse phase and dimethicone or cyclopentasiloxane as the continuous phase. Among the emulsifiers studied only silicone surfactants (cyclomethicone/dimethicone copolyols) which were miscible in silicone oil stabilized the emulsions. Cyclomethicone/PEG/PPG-18/18 Dimethicone and Cyclopentasiloxane/PEG/PPG-18/18 Dimethicone were more effective in lowering the interfacial tension between castor oil and both dimethicone and cyclopentasiloxane. Emulsions formulated using either of these two surfactants were found to be stable against phase separation and exhibited least globule growth over 168 h. The average particle size was found to be 2-6 microm in these systems formed by probe sonication. Slow release patterns of 3H-dehydroepiandrosterone (DHEA) and 3H-dexamethasone solubilized in the disperse castor oil phase into an aqueous dialyzing medium were observed over 48 h.