A Means of Establishing and Justifying Binary Ethanol/Water Mixtures as Simulating Solvents in Extractables Studies

Although ethanol/water mixtures are frequently used as simulating solvents in extractables studies, it is difficult to establish and justify what the right proportion of ethanol is for a particular drug product. A solvent strength model has been developed based on the leaching behavior of a model compound, di-(2-ethylhexyl) phthalate (DEHP), from a reference source material, plasticized poly-(vinyl chloride) (PVC). By measuring the level of DEHP leached into a drug product from the reference source material, one can use the model to calculate the correct ethanol proportion in the simulating solvent.Using this approach, ethanol/water proportions have been obtained for certain drug products. Additionally, the leaching profiles for DEHP obtained in this study were noted to be consistent with such profiles for other extractables from the PVC reference source material and with other investigations of ethanol/water as model stimulants.