Chitosan has not been able to be formulated as sustained-release crosslinked/coacervated drug carrier in the form of spheroids prepared by extrusion-spheronisation technique. This study re-visits chitosan spheroids and their drug (water-soluble chlorpheniramine maleate) release profiles as a function of crosslinking reaction and coacervation between chitosan, tripolyphosphate salt and alginate under the influences of pH and/or microwave irradiation. Crosslinking of chitosan or chitosan-alginate with tripolyphosphate ions, aided by acidifiers or microwave, did not retard spheroid drug release as a result of low levels of chitosan-tripolyphosphate ionic complexation, high leaching levels of sodium ions of tripolyphosphate salt as channeling agent and porous microstructure of spheroids undergoing acidification or microwave drying. Compositing of tripolyphosphate-free chitosan with alginate (weight ratio of chitosan to alginate at 0.9) however reduced the propensity of drug release, with the initial phase of drug release retardation brought about by alginate, and the late phase by chitosan. The introduction of alginate decreased the prompt disintegration tendency of chitosan spheroids. The availability of chitosan reduced the gradual erosion property of alginate. The availability of chitosan and alginate in the same matrix retained the microstructure of spheroids. The inter-spheroid coacervative bondings between the adjacent chitosan and alginate molecules resulted in spheroid aggregation, reduced the specific surface area for dissolution and further lowered the extent of drug release. Sustained-release chitosan-alginate spheroids can be prepared by extrusion-spheronisation technique through omitting crosslinking agent with channeling agent behavior, acidifier and/or microwave drying. (C) 2019 Elsevier B.V. All rights reserved.