In this work, second derivative spectrophotometry was applied for determining the partition coefficients (K(p)s) of four non-steroidal anti-inflammatory drugs (NSAIDs; flufenamic, meclofenamic, mefenamic and niflumic acids) into human erythrocyte ghost (HEG) membranes over a temperature range from (283.2 to 313.2) K. The proposed method allowed the evaluation and direct analyses of thermodynamic parameters; enthalpy (Delta H-W -> M), Gibbs energy (Delta G(W -> M)) and entropy (Delta S-W -> M) changes of the partitioning of NSAIDs into HEG membranes. The partitioning of NSAIDs between polar aqueous phase and non-polar lipid bilayer HEG membrane phase was exothermic with negative (Delta H-W -> M) which compensated for the changes in (Delta S-W -> M). The negative values of (Delta G(W -> M)) revealed that the partitioning of NSAIDs into HEG, owing to their transfer from polar aqueous phase and non-polar HEG phase is spontaneous. The enthalpy-entropy correlation analysis resulted in a good linearity that suggests an identical partitioning enthalpy-entropy driven compensation mechanism for the studied NSAIDs. (c) 2013 Elsevier Ltd. All rights reserved.