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The purpose of this study was the development of sustained-release lyogel of chlorhexidine in the treatment of periodontal diseases. A sustained-release chlorhexidine lyogel (CHX-G) was formulated, based on Eudragit® (1~3%), polyvinyl pyrrolidone (PVP) (0~10%), triacetin (20~40%), hydroxy ethyl cellulose (HEC) (1%) and glycerin. In vitro studies were performed to determine the release rate of chlorhexidine from CHX-Gs using dialysis tube. Our results suggest that the release rate of chlorhexidine from lyogel could be controlled by changing the lyogel compositions.