Solubility of Ursolic Acid in Aqueous and Non-aqueous Solvents

Solubility of Ursolic Acid in Aqueous and Non-aqueous Solvents

Kamola Tolliboeva, Virginia Commonwealth University
Philip M. Gerk, Virginia Commonwealth University School of Pharmacy


Ursolic acid (UA) is a lipophilic acid that is widely found in different natural sources like the foods, fruits, herbs, and plants we consume [1,2,3]. Ursolic acid is not a new compound in terms of its use, its range of biological roles serving as an antioxidant, anti-inflammatory, antibacterial, and anti-cancer compound have already been established [3,4]. Recent studies have shown promising results in the use of ursolic acid as a potential therapeutic approach in treating obesity, glucose intolerance, and fatty liver diseases [1] due to its ability to decrease body fat and muscle loss, and increase muscle gain in rodents. Such effects are not always associated with disease but come naturally with aging. Therefore, ursolic acid holds a promising potential in helping prevent and limit such effects.

In administering ursolic acid orally, the goal is to deliver it to different organ systems which can be achieved when ursolic acid reaches the bloodstream. However, there are several issues ursolic acid faces due to its properties and one of them is solubility. As previously mentioned, ursolic acid is a highly lipophilic acid making it extremely difficult to pass through biological membranes easily and rapidly. Instead, it’s partitioned and retained in the membranes contributing to its low permeability which was even demonstrated across Caco-2 cells [6]. Low permeability of ursolic acid decreases the amount of the administered dose reaching the bloodstream, therefore, minimizing its oral bioavailability.

In order to maximize the benefits of the ursolic acid, we must first understand the properties that contribute to its low oral bioavailability. In this research project, we specifically targeted the solubility of ursolic acid in different solvent systems. The goal of the research project was to establish a method for analyzing ursolic acid in diverse solvents and determining the solubility of ursolic acid in non-aqueous and aqueous solvent systems. We found ammonium hydroxide and sodium hydroxide to be the best aqueous additives, and 1-octanol to be the best non-aqueous solvent. The end goal is to design an oral dosage form to deliver ursolic acid.