Mechanism Governing Microparticle Morphology during Precipitation by a Compressed Antisolvent:  Atomization vs Nucleation and Growth

Abstract

This study provides insight into the mechanisms that govern morphology in microparticles processed using precipitation by a compressed antisolvent. We explore the time scale of surface tension evolution in jets of miscible fluids injected into critical and near-critical solvents to determine whether the jets atomize into droplets or simply evolve as gaseous plumes. Classical jet breakup length equations, modified with timedependent surface tension, accurately predict observed breakup lengths over a range of liquid miscibilities. Linear jet breakup theory can be applied successfully to near critical conditions. The aerodynamic reduction factor remains constant over a wide range of pressures. However, under miscible conditions, calculations show that surface tension in a 10-cm/s round jet of methylene chloride in carbon dioxide at 8.5 MPa and 35°C approaches 0.01 mN/m in 1 µm. Because this distance is shorter than characteristic breakup lengths, distinct droplets never form. Rather, the jets spread in a fashion characteristic of gaseous jets, whose mixing is well described by the gaseous fluid mixing theory. Presumably, microparticle formation results from gas phase nucleation and growth within the expanding plume, rather than nucleation within discrete liquid droplets.

Effect of supercritical fluid density on nanoencapsulated drug particle size using the supercritical antisolvent method

“…13,14 The TEM images revealed the encapsulation of paracetamol inside biodegradable polymer, as shown in Figure 6. For personal use only.…”

Hydrodynamics Influence on Particles Formation Using SAS Process

“…Lengsfeld et al were the first group that investigated fluid dynamics of the SAS process, studying the evolution and disappearance of the liquid surface tension of fluids injected in supercritical carbon dioxide. They concluded that a gas-like jet is formed after the jet break-up (Lengsfeld et al, 2000). In this way, Kerst et al determined the boundaries between the different modes and they noted a strong interdependence between mass transfer and fluid dynamics (Kerst et al, 2000).…”

Tailoring Particle Microstructures via Supercritical CO₂ Processes for Particular Drug Delivery

“…Lengsfeld et al [86] developed a method for predicting dynamic surface tension and combined this method with linear jet breakup equations to accurately predict jet breakup lengths in immiscible to highly miscible systems. For highly miscible systems, they proposed that microparticle formation results from gas-phase nucleation and growth within the expanding plume, rather than by nucleation within discrete liquid droplets.…”