Production of Fluorocarbon Loaded Lipid Nanoparticles: Design and Experiments

6 Introduction In this thesis the production of Acoustically Active Liposomes (AAL) for pharmaceutical applications with the Particles From Gas Saturated Solutions (PGSS) process have been investigated. Chapter 1 contains an introduction and the state of art of the PGSS and other supercritical- based micronization processes, of the Solid Lipid Nanoparticles (SLN) and the Acoustically Active Liposomes (AAL). In Chapter 2 a new continuous PGSS plant has been developed and designed, in order to process greater amounts of Lipids with respect to the existing apparatus. Among different configurations, a static mixer was selected. The equipment has been sized and its overall performance has been estimated. In chapter 3, by using Fluent ® 6.2 Computational Fluid Dynamics (CFD) software the effect of the main geometric parameters in the performance of the atomizer were investigated and the atomizer unit has been redesigned accordingly, in order to improve the air distribution, diffuser geometry and air liquid contact geometry. In chapter 4 the performance of a CO 2 volumetric pump, ought to be used in the new PGSS plant, has been checked and the air flow out of the nozzle and in the diffuser were measured. A number of PGSS experiments have been accomplished, in the existing apparatus, with the aim to encapsulate water and a perfluorocarbon (PFC) mixture in a mixture of tristearin and phosphatidylcholine (50:50 w/w). Measurements in a Klinger view cell showed that the water-lipid mixture does not melt at all, while the PFC-Lipid one forms two liquid phases. The PFC encapsulation has been quantified through Gas Chromatography-Mass Spectrometry (GC-MS) resulting in a low encapsulation value, even when using castor oil in the mixture. SEM images showed that the particles obtained exhibit many open/porous structures, thus confirming the low PFC encapsulation results. The particle size measurements with Light Scattering showed a particle size ranging from 500-700 nm. The low encapsulation efficiency has been attributed to both the insufficient phase dispersion of the two fluids at the atomizer and the evaporation of PFC due to the stripping effect of CO 2 .