Semipermeable containers typically allow water to diffuse upon storage. The water diffusion rate of the widely distributed X-ray contrast agent Visipaque in polypropylene bottles and MR contrast agent Omniscan in polypropylene syringes has been evaluated. The goal was to develop a mathematical method for estimating the rate constant for water diffusion through the polypropylene wall as a function of several variables. The method presents an opportunity to measure the effect of the variables influencing product stability and thereby predicting the shelf-life at an early stage of the stability study. The effect of temperature, humidity, surface area, wall thickness, concentration of active ingredient and fill volume on the logarithmic rate constant for diffusion was estimated by partial least squares regression. The predictive ability of the cross-validated models was good (r = 0.99) for the two contrast agents. The models were used to predict shelf-life for relevant combinations of temperature and humidity, for the four defined climatic zones.