Amoxicillin trihydrate suits to be encapsulated into a modified matrix to increase its bioavailability. In this study, the effect of drug loading methods on drug dissolution mechanism from chitosan-poly(N-vinylpyrrolidone) hydrogel with CaCO3 as the effervescent agent has been studied. It was found that the encapsulation efficiency of in situ and post loading methods were 93% and 75%, respectively. The dissolution values were 94% and 98%, respectively for in situ and post loading. The dissolution test data was incorporated into zero-order, first-order, Higuchi and Korsmeyer-Peppas models to evaluate the kinetic and the mechanism of the drug dissolutions. The in situ loading method fits well to first-order model (R2 = 0.9772), while the post loading method fits well to Higuchi model (R2 = 0.9880). Based on Korsmeyer-Peppas model, the dissolution mechanism of in situ loading was Fickian diffusion (n = 0.4024), while post loading was a combination of diffusion and erosion (n = 0.5532). From the SEM images, it showed that the surface and cross-sectional of the post loading method hydrogel formed pores and pore channels, both before and after the dissolution test. Meanwhile, on the surface and the cross-sectional of in situ loading method hydrogel had pores and pore channels only after dissolution test.