Hydrogels have attracted great attention because of their excellent potential in application in the area of pharmaceutical research. A series of pH-sensitive hydrogels-poly (methacrylic acid) PMAA and temperature dependent poly (ethylene glycol) (PEG) hydrogels were synthesized and were characterized by the effect of pH on swelling and the temperature dependence of equilibrium swelling in aqueous media.The interaction between hydrogel and drugs also has been investigated by using metronadizole, diclofenac, and salicylic acid as model drugs. In this study, the use of solution microcalorimetry Isothermal titration micocalorimetry (ITM) and as investigational tools for hydrogels was assessed. The results showed that solution microcalorimetry possessed the ability to investigate the hydrogel swelling mechanism and interaction with drug.Since calorimetry-solution microcalorimetry and ITM have demonstrated to be useful to investigate the hydrogels, general conclusion have been summarized and prediction about more complicated system based on the knowledge acquired in this work was envisioned in the end of this work.