The effects of CO 2, CHClF 2 and CH 2FCF under pressure on solid lipids were addressed by high-pressure differential scanning calorimeter (HP DSC). In particular, the influence on solid–liquid and solid–solid transitions were investigated for pure tristearin and a mixture of lipids (tristearin–phosphatidylcholine–dioctyl sulfosuccinate). Both of these substances are commonly used for the production of solid–lipid–nano-particles [R.H. Muller, C.M. Keck, Challenges and solutions for the delivery of biotech drugs: a review of drug nanocrystal technology and lipid nanoparticles, J. Biotechnol. 113 (1–3) (2004) 151–170; J.H. Hu, K.P. Johnston, R.O. Williams, Nanoparticle engineering processes for enhancing the dissolution rates of poorly water soluble drugs. Drug Dev. Ind. Pharm. 30 (3) (2004) 233–245; S.A. Wissing, O. Kayser, R.H. Muller, Solid lipid nanoparticles for parenteral drug delivery. Adv. Drug Del. Rev. 56 (9) (2004) 1257–1272]. The experiments were carried at different operating pressures up to 7.0 MPa. The melting and solidification temperatures were measured for six gas–lipid systems. Interestingly, a hysteresis was observed in the solid–liquid and liquid–solid transitions. In addition, the formation of alpha and beta polymorphisms that are typical for lipids, were found to be affected by the system pressure. With regard to the experiments with CO 2, the results indicate a melting point depression as function of the gas pressure, up to 6 MPa. A similar trend to CO 2 was obtained using CHClF 2 at a lower pressure (0.75 MPa), however CH 2FCF 3 exhibits a weaker effect on the melting temperature depression compared to CHClF 2. These results indicate the possibility of processing liquid lipids and similar thermosensitive compounds in gas-assisted micronization processes under mild temperature conditions.