Abstract:

The usual treatment of hypercholesterolemia includes a class of drugs known as statins (simvastatin among them), which inhibit the prodn. 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 2 treatments can be combined, achieving an additive effect. However, both simvastatin and phytosterols are practically insol. in water, and therefore their absorption and activity are low. Nanosized self-assembled structured liq. systems are modified microemulsions that present an alternative pathway for improving the bioavailability of poorly water-sol. drugs. The goal of this study was to solubilize the maximal quantity of both simvastatin and phytosterols in a single, fully dilutable microemulsion system. The authors constructed a water-dilutable liq. 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 sep. in a water-free conc. When simvastatin and phytosterols were solubilized together at a wt ratio of 2.5:1, max. solubilization was obtained with 4.7 wt% simvastatin and 1.9 wt% phytosterols. Structural and anal. methods were applied including rheol., DSC, SD-NMR, SAXS, and cryo-TEM. The water-free "conc." consisted of direct micelles for which propylene glycol served as the hydrophilic phase. Upon water diln., the direct micelles appear to form "lipophilic compds. dispersed in hydrophilic continuous phase". The solubilizates are located in the droplet core and/or at the interface. [on SciFinder(R)]