Solubilization of simvastatin and phytosterols in a dilutable microemulsion system

The usual treatment of hypercholesterolemia includes a class of drugs known as statins (simvastatin among them), which inhibit the production of cholesterol. Another way of reducing cholesterol levels is with the use of phytosterols, which reduce the transport of exogenic cholesterol from the intestine into the blood stream. The two treatments can be combined, achieving an additive effect. However, both simvastatin and phytosterols are practically insoluble in water, and therefore their absorption and activity are low.Nanosized self-assembled structured liquid systems are modified microemulsions that present an alternative pathway for improving the bioavailability of poorly water-soluble drugs. The goal of this study was to solubilize the maximal quantity of both simvastatin and phytosterols in a single, fully dilutable microemulsion system. We constructed a water-dilutable liquid drug delivery system that includes sucrose monolaurate, propylene glycol, and oleyl lactate. This system exhibits high solubilization capacity for both simvastatin (7.0 wt%) and phytosterols (3.5 wt%) when each is solubilized separately in a water-free concentrate. When simvastatin and phytosterols were solubilized together at a wt ratio of 2.5:1, maximum solubilization was obtained with 4.7 wt% simvastatin and 1.9 wt% phytosterols.Structural and analytical methods were applied including rheology, DSC, SD-NMR, SAXS, and cryo-TEM. The water-free “concentrate” consisted of direct micelles for which propylene glycol served as the hydrophilic phase. Upon water dilution, the direct micelles appear to form “lipophilic compounds dispersed in hydrophilic continuous phase”. The solubilizates are located in the droplet core and/or at the interface.

A fully water-dilutable liquid drug delivery system based on sucrose monolaurate, propylene glycol, and oleyl lactate was constructed. Simvastatin and phytosterols were co–solubilized into the nanodroplets.Figure optionsDownload as PowerPoint slideHighlights
► A fully water-dilutable liquid drug delivery system based on sucrose monolaurate, propylene glycol, and oleyl lactate was constructed.
► The water-free “concentrate” consisted of direct micelles for which propylene glycol serves as the hydrophilic phase.
► Simvastatin and phytosterols were co-solubilized at high loads in the droplets’ core/interface and the system remained thermodynamically stable.