286971 Phase Equilibrium Prediction of Different Phospholipids in Supercritical CO2 with Ehanol As a Co-Solvent

Tuesday, October 30, 2012
Hall B (Convention Center )
Luan Ferraz Sr.1, Ramon Nedia1, Islane Santo2, Rosana Fialho2, Gloria Meyberg2 and Elaine Cabral-Albuquerque2, (1)Federal University of Bahia, Salvador, Brazil, (2)Programa de Pós Graduação em Engenharia Industrial, Federal University of Bahia, Salvador, Brazil

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

L. R. C. FERRAZ1, R. G. NEDIA1, I. ESPÍRITO SANTO1, R. FIALHO1, G. M. COSTA1, E. CABRAL-ALBUQUERQUE1

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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