The present invention relates to sterol ester in the form of a tablet that is suitable for reducing cholesterol levels in patient.
Several reports have described the use of plant-sterols (i.e., xcex2-sitosterol) as dietary supplements for the reduction of serum cholesterol levels. It is generally accepted that the sitosterol family of plant sterols reduces serum cholesterol by inhibiting the intestinal absorption of cholesterol. More recently, xcex2-sitosterol""s saturated equivalent, xcex2-sitostanol, has been shown to be more effective in the reduction of intestinal cholesterol absorption. Furthermore, sitostanol itself is virtually unabsorbed, so it does not contribute at all to in vivo serum cholesterol concentration upon consumption. These observations make xcex2-sitostanol an attractive candidate as a dietary supplement for reduction of serum cholesterol levels.
Typically it has been necessary to incorporate the sterol ester in a suitable material such as a margarine, in which the waxy nature of the sterol ester can be tolerated. There have been reports that describe how the esterification of sterols (stanols) to a fatty acid or an edible oil produces a sterol (stanol) ester with improved micelle solubility characteristics. For example, when sitostanol is esterified to edible oil such as rapeseed oil, a wax-like mixture of fatty acid esters with excellent lipid solubility results. These sterol esters are conveniently incorporated into food products such as margarine.
However there is a continuing need for a tableted form of the sterol ester.
The present invention is directed to a solid oral dosage form having a compressed free-flowing powder, which includes an effective amount of sterol, stanol or their corresponding acid ester to reduce cholesterol, about 5 to about 75 milligrams per dosage form of a support with a surface area range of from about 100 to 350 square meters/gram, wherein the sterol, stanol or their corresponding acid ester is in a molten form when loaded onto the support, and a monofunctional surfactant and a polyfunctional surfactant, wherein the polyfunctional surfactant is a polyoxyethylene derivative of the monofunctional surfactant.
The present invention also provides a method for producing a solid oral dosage form that includes heating a sterol, stanol or their corresponding acid ester at a temperature of from about 45 to about 100xc2x0 C. to provide the sterol, stanol or their corresponding acid ester in a molten form, providing a monofunctional surfactant and a polyfunctional surfactant, wherein the polyfunctional surfactant is a polyoxyethylene derivative of the monofunctional surfactant, admixing the molten sterol, stanol or their corresponding acid ester and the monofunctional surfactant and the polyfunctional surfactant to form a sterol, stanol or their corresponding acid ester-surfactant mixture, providing a support with a surface area of from about 100 to about 350 square meters per gram, adding a sufficient amount of the support to the molten sterol, stanol or their corresponding acid ester-surfactant mixture to form a flowable powder, and optionally compressing the flowable powder to form a tablet.