Abstract: An attempt has been made to enhance the solubility and stability of two poorly-soluble drugs, clarithromycin and prednisolone by forming their combinations with three widely consumed non-prescription drugs: paracetamol, caffeine and ibuprofen. For solubility enhancement, three methods; Solution phase studies, solid dispersions and physical mixtures were used. It is seen that paracetamol produced significant enhancement in solubility of both clarithromycin and prednisolone by all the three methods. A comparison of different methods showed that solid dispersion method produced maximum enhancement for both the drugs. However, as compared to clarithromycin, the magnitude of enhancement was smaller in the case of prednisolone. With increase in ionic strength of the medium, a small decrease in solubility was observed in each case. Paracetamol was also found to be most effective combination drug in enhancing the stability of clarithromycin as well as prednisolone.