Development of Polycaprolactone-Based metronidazole matrices for intravaginal extended drug delivery using a mechanochemically prepared therapeutic deep eutectic system.

The engineering of crystalline multi-component drug systems, including cocrystals and salts, is now an established method of modifying the physicochemical properties and dissolution behaviour of an active ingredient. Remarkably, liquid drug systems, including therapeutic ionic liquids and therapeutic deep eutectic solvents (THEDES), remain largely unexplored as an untapped reservoir for drug modification. In this work, the formation of a THEDES containing metronidazole (MET), the preferred first-line treatment for bacterial vaginosis (BV), was explored. The formed THEDES was evaluated for its dissolution behaviour from a simple polycaprolactone (PCL) matrix, in order to achieve an extended release, balanced with an appropriate onset of action, hence offering improved MET intravaginal application. To minimise handling of the liquid THEDES, an end-to-end continuous process that enables feeding of the raw materials in their respective solid forms, and collection of a solidified final formulation is presented. The concurrent THEDES formation and formulation were carried out using a bench scale (approx. 10 g) twin-screw hot melt extruder. The chosen parent reagents have shown sufficiently strong reactivity and resulted in successful and complete conversion to THEDES while in the presence of PCL, during the extrusion process. The formulated THEDES-PCL matrix exhibited significantly improved onset of drug release followed by a controlled delivery of MET over a total 7-day period in SVF, proving itself as a viable alternative to oral therapy.

Water-Tolerant Trifloaluminate Ionic Liquids: New and Unique Lewis Acidic Catalysts for the Synthesis of Chromane.

The first example of triflometallate ionic liquids, named in analogy to chlorometallate ionic liquids, is reported. Trifloaluminate ionic liquids, synthesized from 1-alkyl-3-methylimidazolium triflates and aluminum triflate, were characterized by multinuclear NMR spectroscopy and FT-IR spectroscopy, revealing the existence of oligonuclear, multiply-charged trifloaluminate anions, with multiple bridging triflate modes. Acceptor numbers were determined to quantify their Lewis acidity, rendering trifloaluminate ionic liquids as medium-strength Lewis acids (AN = ca. 65). Used as acidic catalysts in the cycloaddition of 2,4-dimethylphenol and isoprene (molar ratio 2:1) to prepare chromane, trifloaluminate systems outperformed literature systems, showing high activity (conversions 94-99%, selectivities 80-89%) and at low loadings (0.2 mol%) at 35°C. Using these new systems as supported ionic liquid phase (SILP) on multi-walled carbon nanotubes (ionic liquid loading 16 wt%) delivered a recyclable catalytic system, with activity enhanced with respect to the homogenous regime.