(393aw) Phase Equilibrium Prediction of Different Phospholipids in Supercritical CO2 with Ehanol As a Co-Solvent

Ferraz, L. Sr., Federal University of Bahia
Fialho, R., Federal University of Bahia
Nedia, R., Federal University of Bahia
Santo, I., Federal University of Bahia
Meyberg, G., Federal University of Bahia

Equilibrium prediction of different phospholipids in Supercritical CO2
with Ehanol as a Co-solvent.


Programa de Pós graduação em Engenharia Industrial (PEI)

Federal University of Bahia - Brazil.

Over the last decades, diverse types of drug delivery systems have been
under intense investigation. One of them is liposomes, a colloidal association
of amphiphilic lipids that organize themselves
spontaneously in bilayer vesicles as result of unfavorable interactions between
phospholipids and water. As these lipid vesicles present lipophilic and
hydrophilic portions, they can entrap substances with different lipophilicities in the phospholipid bilayer, in the aqueous
compartment or either at the bilayer interface, which can modify
physicochemical properties and can enhance biological activity of entrapped
compounds. A wide variety of conventional techniques exists to produce
liposomes. However, conventional techniques may not be suitable for the
preparation of formulations because involve additional steps such as sonication
or removal of the organic. So, special interest has been given to the application
of supercritical fluid to obtain liposomes due to the
possibility of exploiting the peculiar

properties of supercritical fluids, and
in particular of supercritical carbon dioxide (sc-CO2), the most used
supercritical fluid. Therefore, working with sc-CO2 it is possible to carry out
the process at near-ambient temperatures, avoiding the degradation of thermolabile substances. Additionally, sc-CO2 also provides
an inert medium and eliminates or reduces the use of toxic or contaminant
organic solvents in the process.

Knowledge of description of
the solid-liquid equilibrium involving phospholipids, supercritical
CO2 as solvent and ethanol as co-solvent is essential for the
design of these processes.

                In this study,
the solubility
modeling of different phospholipids (phosphatidylcholine,
phosphatidylglycerol and phosphatidylethanolamine)
in supercritical CO2 and ethanol as co-solvent was analyzed to determine the best
conditions to initialize the process of liposome production. The
thermodynamic model chosen to study the equilibrium between the phospholipids
and the supercritical solvent was the model that uses the Peng-Robinson
equation of state with the LCVM mixing rule and the UNIFAC method (PR-LCVM). In
the literature there is no
information on critical properties, molar volume of
the solid and sublimation pressure of this
solution required in the modeling. Using an alternative
technique, values ​​of those properties were obtained
through group contribution method and showed good agreement with
experimental data using one parameter fit model.

In the present study, predicted results showed that this model enables
the prediction of the solubility of different phospholipids in supercritical carbon
dioxide and ethanol as co-solvent. The results were
very consistent as compared with low solubility data reported
in the literature. In addition, it is also possible to predict solubilities of phospholipids in several temperature and
pressure conditions expanding experimental data.

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