Variability in dissolution rates of cholesterol pellets in bile acid solutions

Large variations in dissolution rate behavior of cholesterol monohydrate pellets may result from small changes in experimental procedures. For example, when cholesterol monohydrate pellets were stored overnight prior to a dissolution run, the initial dissolution rates varied by more than a factor of 2. It is well known that cholesterol monohydrate is converted to anhydrous cholesterol; cholesterol may be unstable toward light. heat, and other radiation in the presence of air, leading to its decomposition. To determine the cause of the variable dissolution rates, experiments were conducted with pellets "aged" under various conditions. The data shown that the probable cause of the variations is the pellet surface conversion of the monohydrate to anhydrous cholesterol, which may take place during pellet storage. The combined effects of temperature and humidity seem to be important. A uniform experimental procedure is needed if investigators hope to reproduce results within their own laboratories as well as reproduce the findings of others.