Studies on a Cholesterol-Lowering Microcrystalline Phytosterol Suspension in Oil

von Bonsdorff-Nikander, A.K., 2005. Studies on a cholesterol-lowering microcrystalline phytosterol suspension in oil Dissertationes bioscientiarum molecularium Universitatis Helsingiensis in Viikki, 2/2005, 55 pp., ISBN 952-10-2289-2 (print) ISBN 952-10-2290-6 (pdf) ISSN 1239-9469 Some cholesterol-lowering drugs have lately caused severe side-effects in humans and the potential use of phytosterols as an optional method of lowering serum cholesterol has been given considerable attention. Although the positive effect of phytosterols has been known for decades, their unpleasant gritty texture and the poor solubility has prevented their widespread use. In the present study, an oral phytosterol suspension was prepared by adding water to a supersaturated sterol in oil solution. The addition of water decreased the solubility in oil and microsized sterol crystals were formed. By changing the amount of sterol and/or water it was possible to control the crystal form, habit and size distribution. In the presence of water phytosterol recrystallised as needle-shaped hemihydrate or monohydrate crystals. Without added water, anhydrous plate-like crystals were achieved. Higher sterol concentrations resulted, due to supersaturation, in the formation of small crystals. By optimised process parameters, i.e. cooling temperature and stirring, it was also possible to achieve the desired crystal size for a so-called creamy suspension. Hardly any changes in crystal habit, size distribution or form were observed during storage of these suspensions for four months. Incorporation of the suspension into cholesterol-lowering products includes heating and thus the knowledge of structural and mechanical changes of the suspension during heating is of importance. Dehydration of phytosterol crystals in an oil suspension was, similarly to plain crystals, a two-phased process. The suspension became less elastic and the crystals started to dissolve at relatively low temperatures. A clinical study performed earlier using a similar microcrystalline suspension revealed a significant reduction of serum cholesterol levels. A dynamic in vitro study was performed to understand the mechanism by which phytosterols can inhibit cholesterol absorption in the small intestine. In addition to phytosterol, the choice of lipid in the suspensions was observed to have a significant effect on the solubilisation of sterols into the mixed micelles. The in vitro studies, in which medium chain length (MCT) and long chain length (LCT) lipids were compared, showed that phytosterols formulated in MCT efficiently displaced cholesterol from mixed micelles. Solubilisation into intestinal mixed micelles is a prerequisite for sterols to reach the site of absorption and thus cholesterol absorption is decreased.