Chitosan-epichlorohydrin hydrogel films (ChitEPI) were synthesized by using chitosan in the presence of epichlorohydrin (EPI) as a crosslinking agent at various amounts. SEM, FTIR, TGA, and DSC analysis were conducted for the characterization of the hydrogels. The DSC measurements indicate that ChitEPI hydrogels did not exhibit better thermal stability when compared to chitosan. Swelling behavior of Chitosan-EPI hydrogel film is pH dependent and showed a reversible swelling behavior with a fast response. The hydrogels were used for in vitro release of promethazine hydrochloride (PHCl) in pH = 1.2 and pH = 7.4 phosphate buffer solutions (PBS). The release of PHCl synthesized from hydrogels at pH = 7.4 is quite low while at pH = 1.2, the highest value was observed as 49% for ChitEPI600. It has been also found that PHCl release from ChitEPI thin films is mainly controlled by diffusion control mechanism. ChitEPI hydrogels may be used for the delivery of drug in stomach and gastrointestinal tract. (c) 2008 Wiley Periodicals, Inc.