For the first time, gas-filled microparticles were successfully prepared using a supercritical fluid based technology. Low molecular weight perfluorcarbon (PFC) gases, C3F8 or C4F8, have been encapsulated into Gelucire (R) 50/13 (lipid-based carrier: polyethylene glycol glycerides), using PGSS (R) (Particles from Gas Saturated Solution) technique. Particles were produced from the fast expansion of the melted lipid carrier saturated with a mixture of (CO2 + PFC). The presence of the gas into the produced microparticles was verified by Nuclear Magnetic Resonance (NMR) analysis of fluorine atom. The effect of carrier to PFC mass ratio and PFC structure on the entrapment efficiency of the PFC gas into the particles was evaluated at fixed at 8.5 MPa and 353 K. These parameters were fixed in a preliminary study according to the morphology, size and flowability of the particles. The stability of encapsulated C4F8 in microparticles showed to be higher than C3F8; it was determined to be 2 h, at room conditions at the optimized carrier: PFC mass ratio of 30:1. (C) 2013 Elsevier B.V. All rights reserved.