Abstract: OBJECTIVE To prepare a 12 h sustained-release clarithromycin (CAM) gastric-floating tablet using semi-solid extrusion based 3D printing technology.METHODS To explore the effect of compound use of pH-sensitive,temperature-sensitive,water-insoluble polymer gel matrix and HPMC K15MCR on the release of CAM,and evaluate the weight variation,hardness,fragility,dissolution curve and dissolution mechanism of CAM gastric-floating sustained-release tablets.RESULTS With the semi-solid extrusion based 3D printing technology,only using HPMC K15MCR as a release blocker could prepare CAM gastric-floating sustained-release tablets with drug loading rate up to 81.7%,and the relevant indicators accessed to the requirement of Chinese Pharmacopoeia 2020 Edition.CONCLUSION The semi-solid extrusion based 3D printing technology has great application potential in preparing gastric-floating sustained-release drug delivery systems.