In light of prediction of extent of drug molecules that cross biological membranes in drug-complex system, there is a need to re-evaluate the old concept of measuring the binding constant of complexation (Kc) and consequently the drug thermodynamic activity (AT) through octanol-water partition experiment or solubility technique at saturation condition. This study examined the feasibility of the silicone polymer uptake method for determination of AT of corticosterone (CS)-as a model lipophilic drug-in hydroxypropyl beta cyclodextrin (HP  CD). Commercial medical grade silicone rubber sheets were used first in the study then replaced by prepared silicone discs to ensure the validity of CS partition data obtained in silicone/phosphate buffered saline (PBS) system in absence and presence of HP  CD. In cases of saturation and unsaturation with trace level radioactive corticosterone (3H-CS), the Kc was measured. It was the same at saturation as well as lower drug concentration, and in correlation with that measured by solubility technique at saturation. However, the Kc measured by silicone method deviated from that obtained from octanol/ phosphate buffered saline partition experiment due to possible interaction between HP  CD as a complexing agent with lipophilic cavity and the organic phase (octanol). The measured AT values were in agreement with those determined by octanol and solubility methods. This study has clearly shown the validity of the silicone polymer uptake method for the direct determination of CS thermodynamic activity in CS/ HP  CD inclusion complex