In contrast to antisolvent techniques, the DELOS process takes advantage of the cosolvent behavior that CO2 presents over solutions of active drugs and polymers in certain organic solvents. In this method, the CF is added to an organic solution of the compound(s) to precipitate, resulting in a new pressurized solution (P ≤ 10 MPa), in which the solvent medium is formed by the mixture ‘organic solvent/CF’. The rapid evaporation of the CF upon depressurization of the solution generates an abrupt, fast and homogeneous cooling that provokes the straightforward precipitation of the solute as micro- or nano-particles. The supersaturation profiles achieved by this process are very high and reproducible in every point of the cooled solution allowing the achievement of nanoscopic particles with a narrow size distribution. DELOS has been used for the successful micronization of drugs, such as aspirin, ibuprofen, acetaminophen and naproxen , and biodegradable polymers such as poloxamers. Although less explored than antisolvent techniques, DELOS offers some advantages such as less consumption of CO2, easier scalability due to the lack of nozzles and the filtration step at atmospheric pressure.

The DELOS process, based on the use of compressed fluids, is an efficient crystallization method for the one step production of crystalline micron-sized particles of active pharmaceutical ingredients with high polymorphic purities and no detectable residual solvent content by TGA. In addition, the actual particle size of the processed powders can be modulated by controlling operational parameters, such as the CO2 content of the expanded solution, and the concentration of the initial solution. The influence of these process parameters on nucleation rates and on products characteristics can be predicted from solubility data through the methodology presented here for the first time. This new process can provide real advantages over conventional crystallization processes, such as (1) high purity products, (2) control of crystal polymorphism, (3) in-process elimination of residual solvent/reduction of residual solvent levels, (4) processing of thermolabile and waxy compounds, (5) single-step in single-area process, (6) easy and reproducible scale-up (7) environmentally friendly technology (8) technically and economically viable process at industrial scale.


To see more about DELOS process:

  • Crystallization of micro-particulate pure polymorphs of active pharmaceutical ingredients using CO2-expanded solvents
    Cryst. Growth Des. 2012, 12, 1717−1726
    Santiago Sala, Alba Cordoba, ́Evelyn Moreno-Calvo, Elisa Elizondo, Maria Munto, Paula Elena Rojas, Maria Àngels Larrayoz, Nora Ventosa, Jaume Veciana


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