The Effect of System Temperature and Pressure on the Fluid-Dynamic Behavior of the Supercritical Antisolvent Micronization Process: A Numerical Approach

Abstract

-The Supercritical Antisolvent (SAS) technique allows for the precipitation of drugs and biopolymers in nanometer size in a wide range of industrial applications, while guaranteeing the physical and chemical integrity of such materials. However, a suitable combination of operating parameters is needed for each type of solute. The knowledge of fluid dynamics behavior plays a key role in the search for such parameter combinations. This work presents a numerical study concerning the impact of operating temperature and pressure upon the physical properties and mixture dynamics within the SAS process, because in supercritical conditions the radius of the droplets formed exhibits great sensitivity to these variables. For the conditions analyzed, to account for the heat of mixture in the energy balance, subtle variations in the temperature fields were observed, with almost negligible pressure drop. From analyses of the intensity of segregation, there is an enhancement of the mixture on the molecular scale when the system is operated at higher pressure. This corroborates experimental observations from the literature, related to smaller diameters of particles under higher pressures. Hence, the model resulted in a versatile tool for selecting conditions that may promote a better control over the performance of the SAS process.

Single step encapsulation process of ivermectin in biocompatible polymer using a supercritical antisolvent system process

“…The production of lecithin/PMMA NPs formulated with IVM was performed in the Super Particle SAS Model 200 (Thar SFC, USA) equipment (Figure 1) according to our previous study 20 . A 30 mg of polymer (PMMA) per milliliter of solvent (DCM) and 10% of the drug in relation to the polymer by weight was used 12,20 . Different lecithin concentrations, varying from 10% to 30% in relation to the polymer (PMMA) were evaluated.…”

“…The solution was only injected after the expansion/precipitation vessel reached both the operational pressure (9 MPa) and temperature (40°C). The solution expanded in a coaxial regime through a 180‐μm diameter capillary tube of fused silica 12,21 …”

“…The nanoparticles formation process via SAS technique allows the drug/capsule complex to precipitate in the equipment due to rapidly expansion of the organic solvent. The organic polymers are typically insoluble in supercritical CO 2 12 . The precipitation process occurs due to the antisolvent effect of CO 2 in supercritical conditions, which results in the loss of interaction of the supercritical solvent + organic solvent mixture and the precipitated solute.…”

Analysis of the Mechanism of Cholesterol Particle Formation by Liquid Antisolvent Crystallization

“…The solute supersaturation thus attained, in turn, leads to nucleation and subsequent growth of the particles. The antisolvent can be in the form of a supercritical fluid (SCF), such as supercritical carbon dioxide (ScCO 2 ), or a gas such as CO 2 , − or a liquid such as water . The general principles and fundamentals of particle engineering using supercritical fluids, and their diverse applications have also been reviewed comprehensively by Tabernero et al Specific applications of gas antisolvent (GAS) processes in the domain have also been presented by Elvassore et al and Zodge et al, while those of the supercritical fluid antisolvent (SAS) have been reviewed by Reverchon et al and Franco and De Marco …”

Liquid-liquid Mixing in Y-type Microchannel

“…The objective of mixing is to decrease inequalities and uneven of solute composition in a mixture of two components and to change the fluid flow from heterogeneous to more homogenous condition. By that way, the fluid in the flow becomes less non-uniform by dilute the concentration, density, temperature and others (Almeida et al 2016). As well, the mixing behavior is studied to understand of flow structure of process and mixing mechanism (Rudyak et al 2014) in the system.…”