It has recently been found that lipid composition appears to have a major influence on the rate of lipase-induced degradation of lipid-based extended release drug delivery systems (microparticles, compressed implants and extrudated implants). Previously, we have found that during lipase incubation, depending on the lipid used, lipidic extrudates can lose their physical strength and collapse generating lipid particles in the μm-range. The aim of this study was to characterise the processes leading to collapse of solid lipid-based drug delivery systems during in vitro lipase incubation. Compressed lipid implants were used as model systems. Free fatty acids (FFA) generated in the incubation experiments were derivatised and subsequently analysed via reversed phase-HPLC in order to characterise the degradation behaviour of single lipid components (glyceryltrilaurate (D112), glyceryltrimyristate (D114), glyceryltripalmitate (D116) and glyceryltristearate (D118)) used for the preparation of compressed lipid implants. Further, Raman spectroscopy/microscopy, differential scanning calorimetry, scanning electron and light microscopy were used to investigate the physical and chemical changes in the implants upon lipase incubation. This study revealed that the lipid component D112 plays a major role in the degradation and erosion processes occurring during lipase incubation of lipid implants. The production of D112/lauric acid mixtures, with a melting point below human body temperature, leads to lipid matrices melting and losing their physical integrity.