Production of carrier/antioxidant particles by Supercritical Assisted Atomization as an adjuvant treatment of the CoVID-19 pathology
The 2019 coronavirus outbreak caused a global health emergency. Some therapeutic strategies for this pathology focus on natural compounds, such as flavonoids, because of their antimicrobial and antiviral properties. However, the therapeutic efficacy of these active compounds is limited by their low bioavailability. In this paper, composite systems consisting of the flavonoid and a carrier were produced by Supercritical Assisted Atomization to increase these compounds' dissolution rate. Luteolin, rutin, and naringenin were selected as model flavonoids, and hydroxypropyl-β-cyclodextrin and polyvinylpyrrolidone were chosen as the carriers. Hydroxypropyl-β-cyclodextrin was the most suitable carrier, in terms of recovery, morphology/size of the particles, and dissolution rate of the active compound. At the best operating conditions, the dissolution rate of the active principle is speeded for all the flavonoids: in particular, if compared to the virgin materials, it is 55.8 times faster for luteolin, 3.1 times faster for rutin and 3.4 times faster for naringenin.
Solubility of favipiravir (as an anti-COVID-19) in supercritical carbon dioxide: An experimental analysis and thermodynamic modeling
Favipiravir is one of the most commonly prescribed drugs in the treatment of COVID-19 in the early stages of the disease. In this work, the solubility of favipiravir was measured in supercritical CO at temperatures ranging from 308 to 338 K and pressures ranging from 12 to 30 MPa. The mole fraction solubility of favipiravir was in the range of 3.0 × 10 to 9.05 × 10. The solubility data were correlated with three types of methods including; (a) density-based models (Chrastil, Garlapati and Madras, Sparks et al., Sodeifian et al., K-J and Keshmiri et al.), (b) Equations of states SRK with quadratic mixing rules) and (c) expanded liquid theory (modified Wilson model). According to the results, modified Wilson and K-J models are generally capable of providing good correlation of solubility. Finally, the approximate values of total ( ), vaporization ( ), and solvation ( ) enthalpies were computed.
Application of Quality by Design to the robust preparation of a liposomal GLA formulation by DELOS-susp method
Fabry disease is a lysosomal storage disease arising from a deficiency of the enzyme α-galactosidase A (GLA). The enzyme deficiency results in an accumulation of glycolipids, which over time, leads to cardiovascular, cerebrovascular, and renal disease, ultimately leading to death in the fourth or fifth decade of life. Currently, lysosomal storage disorders are treated by enzyme replacement therapy (ERT) through the direct administration of the missing enzyme to the patients. In view of their advantages as drug delivery systems, liposomes are increasingly being researched and utilized in the pharmaceutical, food and cosmetic industries, but one of the main barriers to market is their scalability. Depressurization of an Expanded Liquid Organic Solution into aqueous solution (DELOS-susp) is a compressed fluid-based method that allows the reproducible and scalable production of nanovesicular systems with remarkable physicochemical characteristics, in terms of homogeneity, morphology, and particle size. The objective of this work was to optimize and reach a suitable formulation for in vivo preclinical studies by implementing a Quality by Design (QbD) approach, a methodology recommended by the FDA and the EMA to develop robust drug manufacturing and control methods, to the preparation of α-galactosidase-loaded nanoliposomes (nanoGLA) for the treatment of Fabry disease. Through a risk analysis and a Design of Experiments (DoE), we obtained the Design Space in which GLA concentration and lipid concentration were found as critical parameters for achieving a stable nanoformulation. This Design Space allowed the optimization of the process to produce a nanoformulation suitable for in vivo preclinical testing.
Supercritical carbon dioxide application using hydantoin acrylamide for biocidal functionalization of polyester
Biocidal functionalization in polyester fibers is a really tough challenge because of the lack of tethering groups. This study indicated supercritical carbon dioxide application using -halamine would be an alternative solution for obtaining antibacterial function on the polyester surface. Firstly, -(2-methyl-1-(4-methyl-2,5-dioxo-imidazolidin-4 yl)propan-2 yl)acrylamide was synthesized and applied to the polyester in supercritical carbon dioxide medium, at 120 °C, 30 MPa for different processing times. The addition of -halamine on the surface significantly brought antibacterial activity against . The chlorine loadings showed that 6 -h exposure time was critical to obtain sufficient antibacterial activity. This treatment caused a reasonable and tolerable loss in color and mechanical properties. But, the durability to abrasion, stability, and rechargeability of oxidative chlorine, and the durability of -halamine on the surface were remarkably good. Conclusively, it can be available to work on polyester surfaces with resource-efficient and eco-friendly supercritical carbon dioxide technique for getting more functionalization and modification.
Equation of state and thermodynamic properties for mixtures of , , , and from ambient up to 1000 K and 280 MPa
Supercritical water oxidation (SCWO) is an effective technique to treat wet organic wastes. Its modeling requires an accurate calculation of thermodynamic properties. In this work an equation of state (EOS) is proposed which accurately predicts the thermodynamic state of mixtures of water, oxygen, nitrogen, and carbon dioxide for a wide range of compositions, temperatures, and pressures including supercritical conditions. The EOS includes a volume translation, an evolved -function and non-quadratic mixing rules. The introduced parameters are regressed to experimental data. From the pressure-explicit EOS, enthalpy, specific heats at constant volume and constant pressure, and fugacity coefficients are derived and calculated. The binary mixtures , , , as well as the ternary mixture are well predicted by the proposed EOS with relative errors below 10% and 15%, respectively. The region of low temperature and high pressure is most difficult to predict with relative errors up to 20%.
Hydrothermal Ethanol Flames in Co-Flow Jets
Results on the autoignition and stabilization of ethanol hydrothermal fames in a Supercritical Water Oxidation (SCWO) reactor operating at constant pressure are reported. The flames are observed as luminous reaction zones occurring in supercritical water; i.e., water at conditions above its critical point (approximately 22 MPa and 374 °C). A co-flow injector is used to inject fuel (inner flow), comprising an aqueous solution ranging from 20 %-v to 50 %-v ethanol, and air (annular flow) into a reactor filled with supercritical water at approximately 24.3 MPa and 425 °C. Results show hydrothermal fames are autoignited and form diffusion flames which exhibit laminar and/or turbulent features depending upon flow conditions. Two orthogonal camera views are used; one providing a backlit shadowgraphic image of the co-flow jet and the other providing color images of the flame. In addition, spectroscopic measurements of flame emissions in the UV and visible spectrum are discussed.
Removing Endotoxin from Metallic Biomaterials with Compressed Carbon Dioxide-Based Mixtures
Bacterial endotoxins have strong affinity for metallic biomaterials because of surface energy effects. Conventional depyrogenation methods may not eradicate endotoxins and may compromise biological properties and functionality of metallic instruments and implants. We evaluated the solubilization and removal of E. coli endotoxin from smooth and porous titanium (Ti) surfaces and stainless steel lumens using compressed CO(2)-based mixtures having water and/or surfactant Ls-54. The CO(2)/water/Ls-54 ternary mixture in the liquid CO(2) region (25 °C and 27.6 MPa) with strong mixing removed endotoxin below detection levels. This suggests that the ternary mixture penetrates and dissolves endotoxins from all the tested substrates. The successful removal of endotoxins from metallic biomaterials with compressed CO(2) is a promising cleaning technology for biomaterials and reusable medical devices.
Compatibility of Medical-Grade Polymers with Dense CO(2)
This study reports the effect of exposure to liquid carbon dioxide on the mechanical properties of selected medical polymers. The tensile strengths and moduli of fourteen polymers are reported. Materials were exposed to liquid CO(2), or CO(2) + trace amounts of aqueous H(2)O(2), at 6.5 MPa and ambient temperature. Carbon dioxide uptake, swelling, and distortion were observed for the more amorphous polymers while polymers with higher crystallinity showed little effect from CO(2) exposure. Changes in tensile strength were not statistically significant for most plastics, and most indicated good tolerance to liquid CO(2). These results are relevant to evaluating the potential of liquid CO(2)-based sterilization technology.