Different interpolymer complexes (IPCs) of chitosan (CS) and carboxymethylcellulose sodium salt (CMC) were used to elaborate mini-matrices containing clarithromycin (CAM). IPCs were characterized by FTIR, DSC and powder X-ray (XRD). Compression processes did not modify the physical state of CAM which was in its polymorph Form II. However, during tableting, polymer/polymer interactions occurred to form matrix systems that were confirmed by DSC. When mini-matrices were placed in acetate buffer (pH 4.2), the formation of a CAM solvate was determined by XRD, FTIR and DSC, showing the presence of incorporated crystallizing solvent molecules. Grazing incidence X-ray diffraction (GID) enabled us to profile transformations of CAM on surfaces of mini-matrices when it is in intimate contact with dissolution medium, and its conversion to a solvate form prior to its dissolution process. Besides, FTIR and DSC revealed polymer-polymer electrostatic interactions during dissolution process. Furthermore, swelling and eroding studies and in vitro drug release exhibited that when increasing the amount of CS within IPCs, swelling and erosion rates were greater and CAM release was faster. Zero-order kinetics from drug release profiles were related to linear erosion kinetics, and highlighted that erosion played an important role in drug release due to CAM poor solubility at this pH.