Production of liposomes in a multitubular system useful for scaling up of processes

Abstract

This work describes the production of liposomes by hydration of a lipid film formed in a multitubular system. The process is a modified approach of the classical Bangham method, in which a thin lipid film is adsorbed in the inner surface of glass tubes. Initially, continuous adsorption was achieved by feeding a lipid dispersion in ethanol at the bottom of the tubes through a peristaltic pump, and circulating the dispersion for 30 min at 60 °C. In a second step, the excess of lipids was drained and the film was dried under vacuum. The dried film was hydrated using a buffered solution in order to produce liposomes. The adsorption of lipids was characterized through their isotherm and kinetics profiles. The hydration kinetics was monitored by the absorbance of the solutions, the mean diameter and the phospholipid concentrations at different initial concentrations of the lipid dispersion. A heterogeneous population of multilamellar liposomes was produced with a mean diameter of approximately 1,500 nm, as determined by dynamic laser light scattering. The tuberculostatic pyrazinamide was entrapped in liposomes and the incorporation efficiency was higher when the drug was added in the hydration solution (14.7%) than in the phospholipid film (6.7%). The stability profile in the presence of surfactants and the gradual release of the drug confirm the membrane properties of the liposomes produced. The results show the potentialities of the process for continuous production of liposomes and applications in the pharmaceutical industry.