The solubility of pharmaceutical solid compounds in supercritical carbon dioxide is of great importance in a wide range of applications that include: development of drug delivery systems, powder processing, and precipitation/crystallization processes. This manuscript aims to estimate the solubility behavior of pharmaceutical compounds in supercritical fluids using an activity coefficient model based on linear solvation energy relationships. The parameters of this model were further generalized as a function of the properties of the pharmaceutical compounds. The selected compounds include antioxidants, antibiotics, steroids and anti-inflammatory and their solubility data were collected from literature. This model is able to estimate the solubility of the pharmaceutical compounds in supercritical carbon dioxide within acceptable accuracy for more than 60% of the proposed systems. (c) 2011 Elsevier B.V. All rights reserved.