Nanoparticle engineering of drug crystals is an important basic tool for efficient and intelligent drug delivery. Recently, the wet comminution process of drug nanocrystals in the presence of polymeric stabilizers has been successfully developed, but it has not been well understood yet how to select a proper stabilizer for a drug. In this study, the nature of interactions between polymeric stabilizers and drugs was investigated by analyzing the steady state particle sizes of 7 drugs obtained by wet comminution. The surface energy of drugs and polymers measured by contact angle measurement was found to be an important factor, although it could not solely determine the steady state values of particle size. In addition to surface energy, specific interactions between functional groups appeared to play a certain role. The stabilization ability of polymers and the subsequent steady state particle size of drug nanocrystals depend on various parameters including surface energy and specific interactions. (c) 2005 Elsevier B.V. All rights reserved.