The present study aimed to develop and validate an advanced image stitching algorithm integrated with chemical imaging at the nanometre scale. This was applied to track the swelling, erosion, drug release and changes in surface texture of a swelling-controlled release system. The technique involves the delivery and withdrawal of a liquid droplet from the surface of the tablet alongside capturing multiple images of tablet surface using white light profilometry. The recovered liquid was then subject to chemical analysis for the quantification of drug and HPMC. The multiple images acquired during drug release were stitched together using an algorithm developed to generate a full tablet surface. New methods for swelling analysis (regional point, area and multiple regional analysis techniques) were also successfully developed. The results exhibited the exceptional capability of this technique for providing quantitative information regarding swelling, erosion, drug release and surface topography, hence negating the need for separate investigations. Moreover, it can also be anticipated that this technique may have potential use in other fields where surface dissolution, erosion and swelling have significant impact.