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Purpose: The aim of this study was to better understand the underlying drug release characteristics from matrix tablets based on the combination of chitosan (CS) and different types of carrageenans (κ-CG,ι-CG,and λ-CG).Methods: Highly soluble trimetazidine hydrochloride (TH) was used as a model drug.Firstly,characteristics of drug release from different formulations were investigated,and then in situ complexation capacity of CG with TH and CS was studied by differential scanning calorimetry and fourier transform infrared spectroscopy.Erosion and swelling of matrix were also characterized in order to better understand the drug release mechanisms.Effects of pH and ionic strength on drug release were also studied.Results: It was found that not only ι-CG and λ-CG could reduce the burst release of TH by the effect of TH-CG interaction,CS-ι-CG and CS-λ-CG based polyelectrolyte film could further modify controlled release behavior,but not CS-κ-CG.High pH and high ionic strength resulted in faster drug release from CS-κ-CG and CS-ι-CG based matrix,but drug release from CS-λ-CG based tablet matrix was less sensitive to pH and ionic strength.Conclusions: In conclusion,CS-λ-CG based matrix tablets are quite promising as controlled release drug carrier based on multiple mechanisms.