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Co-Precipitation of Beta-Carotene and Bio-Polymer Using Supercritical Carbon Dioxide as Antisolvent
Abstract and Figures
The objective of this work was to investigate the application of supercritical carbon dioxide as antisolvent for the co-precipitation of β-carotene and poly(hydroxybutirate-co-hydroxyvalerate) (PHBV) with dichloromethane as organic solvent. For this purpose, the concentrations of β-carotene (1 to 8 mg.cm-3) and PHBV (20 to 40 mg.cm-3) in the organic solution were varied keeping fixed temperature at 313 K, pressure at 8 MPa, solution flow rate at 1 cm3.min-1 and antisolvent flow rate at 39 g.min-1. The morphology of co-precipitated particles were spherical with very irregular and porous surface for some conditions and very smooth surfaces for others as verified by micrographs of scanning electronic microscopy (SEM). Results show that it is possible to achieve encapsulation efficiency values as high as 35% just manipulating the concentration ratio of solute to polymer in organic solution. The methodology adopted for the quantification of β-carotene encapsulated was demonstrated to be adequate.
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... The different functional groups affect the formation and degree of cross-linking. Biopolymers are the greatest eye-catchers for researchers as compared to synthetic polymers [4] as they are economical, low in toxicity, [5] bio-degradable, [6] easily available, [7] biocompatible, [8] and are easily modifiable. [9][10] These traits not only safeguard our environment [11] but also enhance their applicability in oral drug delivery, [12] medicine, [13] tissue engineering, [14] wastewater treatment, [15] and the agricultural sector. ...
Agronomy inexorably contributes an eminent role in food nutriment and the economic upswing of a country. Micronutrients though required exiguously; are vital for the growth, health, and higher yields of the crops. Micronutrient supplementation at a controlled rate in an economical and eco‐friendly way is the major challenge, an agro‐researcher has to deal with. The potential of scientific research entails the usage of natural, renewable, and abundant raw materials that endow a solution to the agronomical challenges of today's world. Besides being non‐hazardous, biopolymer‐based matrices are pertinent materials that act as a reservoir of micronutrients and are a boon for agronomy, this review explores the synthesis of biomatrices, loading of micronutrients into the bio‐matrix, kinetics, and mechanism of release of micronutrients along with the citations of the biopolymer‐based matrices used till date for the controlled release of micronutrients that would be rewarding for forthcoming research. These green polymeric matrices have been explored a lot for the release of micronutrients iron, copper, and zinc but more research is required for the supplementation of boron, molybdenum, and manganese. The bio‐matrices applied as micronutrient carrier vehicle in agronomy results in enhanced growth, high crop yield, and sustainability.
... This is due to the wide utilization of these materials in electrochemical devices as ways of solving global concerns. These bio-based polymers can be extracted naturally from living organisms [8]. There is agreement that polymer electrolytes with the appropriate conductivity should be developed for use as separators in electrochemical devices because of having relatively high ionic conductivity as intrinsic properties of SPEs [9,10]. ...
This work presents the fabrication of polymer electrolyte membranes (PEMs) that are made of polyvinyl alcohol-methylcellulose (PVA-MC) doped with various amounts of ammonium iodide (NH4I). The structural and electrical properties of the polymer blend electrolyte were performed via the acquisition of Fourier Transform Infrared (FTIR) and electrical impedance spectroscopy (EIS), respectively. The interaction among the components of the electrolyte was confirmed via the FTIR approach. Electrical impedance spectroscopy (EIS) showed that the whole conductivity of complexes of PVA-MC was increased beyond the addition of NH4I. The application of EEC modeling on experimental data of EIS was helpful to calculate the ion transport parameters and detect the circuit elements of the films. The sample containing 40 wt.% of NH4I salt exhibited maximum ionic conductivity (7.01 × 10−8) S cm−1 at room temperature. The conductivity behaviors were further emphasized from the dielectric study. The dielectric constant, ε’ and loss, ε’’ values were recorded at high values within the low-frequency region. The peak appearance of the dielectric relaxation analysis verified the non-Debye type of relaxation mechanism was clarified via the peak appearance of the dielectric relaxation. For further confirmation, the transference number measurement (TNM) of the PVA-MC-NH4I electrolyte was analyzed in which ions were primarily entities for the charge transfer process. The linear sweep voltammetry (LSV) shows a relatively electrochemically stable electrolyte where the voltage was swept linearly up to 1.6 V. Finally, the sample with maximum conductivity, ion dominance of tion and relatively wide breakdown voltage were found to be 0.88 and 1.6 V, respectively. As the ions are the majority charge carrier, this polymer electrolyte could be considered as a promising candidate to be used in electrochemical energy storage devices for example electrochemical double-layer capacitor (EDLC) device.
In this work, a plant-based resin gel polymer electrolyte (GPE) was prepared by stereolithography (SLA) 3D printing. Lithium perchlorate (LiClO4) with a concentration between 0 wt.% and 25 wt.% was added into the plant-based resin to observe its influence on electrical and structural characteristics. Fourier transform infrared spectroscopy (FTIR) analysis showed shifts in the carbonyl, ester, and amine groups, proving that complexation between the polymer and LiClO4 had occurred. GPEs with a 20 wt.% LiClO4 (S20) showed the highest room temperature conductivity of 3.05 × 10−3 S cm−1 due to the highest number of free ions as determined from FTIR deconvolution. The mobility of free ions in S20 electrolytes was also the highest due to greater micropore formation, as observed via field emission scanning electron microscopy (FESEM) images. Transference number measurements suggest that ionic mobility plays a pivotal role in influencing the conductivity of S20 electrolytes. Based on this work, it can be concluded that the plant-based resin GPE with LiClO4 is suitable for future electrochemical applications.
The leather industry generates approximately ten million tons of solid bio-wastes that can be used to synthesize various multifunctional materials with exciting properties. One such approach involves developing advanced hybrid materials, which is considered one of the key areas but the underdeveloped materials science discipline. This work explored methods to use collagen derived from leather industry bio-wastes to form hybrid films via two different ways: to produce luminescent carbon dots (Cdots) and develop hybrid films. The polymeric collagen was mixed with Cdots and reduced graphene oxide (rGO) to create flexible composite films that exhibit improved thermal, mechanical, electrical, and luminescent properties. The Cdot films displayed enhanced luminescence. The Kubelka-Munk transformation of the diffuse reflectance reveals a massive increase in absorbance in the visible light region with the addition of rGO. Besides, the developed films displayed electrical conductivity and weak ferromagnetic characteristics and showed enhanced biocompatibility. These findings highlight new avenues for converting industrial bio-wastes into useful multifunctional materials in scalable and inexpensive ways, thereby diminishing environmental pollution and enhancing environmental sustainability.
β-Carotene (β-CA) is largely used antioxidant with a high sensibility to oxidation when in contact with light and temperature. To improve its shelf life and develop a nutraceutical formulation it was encapsulated into poly-lactic-co-glycolic acid (PLGA) and poly-lactic acid (PLA) carriers using Supercritical Emulsion Extraction (SEE). α-Tocoferol (α-TOC) and Rosmarinic Acid (RA) were proposed as excipients to improve product shelf-life. Different emulsion formulation conditions, such as compositions and mixing rate were used; whereas, SEE operating conditions in the counter-current tower were fixed at 80 bar and 38 °C with an L/G ratio of 0.1. In these conditions, PLA and PLGA carriers with sizes ranges between 1.5 ± 0.5 μm and 0.3 ± 0.1 μm were fabricated with Encapsulation Efficiencies (EEs) between 50–80%. The co-encapsulation of α-TOC with β-CA gained to prolonged drug shelf life; whereas, RA co-encapsulation was not successfully and, in some cases, also reduced β-CA-EE. The poor loading experienced, in the case of RA, was probably due to its high solubility into the high-pressure mixture of carbon dioxide and organic solvent formed during the emulsion extraction. This behaviour was defined “co-extraction effect” and may limit the application of SEE technology in the encapsulation of molecules soluble in the mixture obtained during oily phase extraction. Shelf-life studies were performed after UV irradiation for ten days and after carriers storage for 2 years at 4 °C. The better performance in terms of shelf life was observed for PLGA capsules loaded with β-CA/α-TOC; whereas, PLA formulation with β-CA/α-TOC showed a superior antioxidant activity with an half minimal Inhibitory Concentration (IC50) against the free radical DPPH of 1.8 mg/mL of carriers.
In this work, Supercritical Antisolvent (SAS) technique is proposed to incorporate ketoprofen (KET), a poorly water-soluble anti-inflammatory drug with analgesic and antipyretic properties, within polyvinylpyrrolidone (PVP), a biocompatible and biodegradable polymer. In order to obtain micrometric particles with controlled dimensions, operating pressures in the range 90–150 bar, concentration of PVP/KET mixture in DMSO from 10 to 100 mg/mL, and PVP/KET ratio from 3:1 to 20:1 were used. Composite spherical microparticles with mean diameters ranging from 2.41 (±1.29) and 3.81 (±2.01) μm were successfully produced, at different operating
conditions. Some analytical techniques, such as differential scanning calorimetry, Fourier transform infrared spectroscopy and UV–vis spectroscopy, were used for the powders' characterization. An increase in the drug dissolution rate in the coprecipitated particles of about 4 times with respect to the unprocessed KET was measured.
In this work, we reported preparation of melatonin-loaded zein nanoparticles using the technique of solution-enhanced dispersion by supercritical CO2 (SEDS) for prolonging the release of melatonin. The influence of pressure, temperature and the ratio of melatonin and zein on the morphology, the particle size and drug loading was investigated. The release profiles of the melatonin-loaded nanoparticles were evaluated. The sizes of the most particles were less than 100 nm at most conditions examined, and the morphology had three types: rod-like, globule, and filament. The maximum drug loading of 6.9% and encapsulation efficiencies of 80.2% were obtained, respectively, under different conditions. The release speed of the melatonin in the nanoparticles is lower than both the pure one and that in the physical mixture. It displayed a near zero-order release which implied that it could be applied as a potential controlled-release drug.
Nimesulide (NIM) is an anti-inflammatory drug, widely used in the treatment of acute pain associated with different diseases. A major limitation in its usage is due to its reduced solubility in water; therefore, large doses are required to reach the therapeutic level, with consequent undesired effects on patient’s health. In order to improve NIM dissolution rate, a possible solution is represented by its micronization. Traditional micronization techniques show several drawbacks: lack of control over the particle morphology and particle size distribution, large solvent residues and use of high temperatures. An alternative to conventional techniques is represented by supercritical carbon dioxide (scCO2) based processes. In particular, nanoparticles and microparticles of different kind of materials were successfully obtained by supercritical antisolvent (SAS) precipitation. However, when processed using SAS, nimesulide precipitated in form of large crystals or it is completely extracted by the mixture solvent/antisolvent. A solution to this problem can be the production of drug-polymer composite microspheres, using a water soluble polymer in which the drug is entrapped. In this work, NIM coprecipitation with polyvinylpyrrolidone (PVP) is proposed on pilot scale. The effects of polymer/drug ratio, concentration, pressure and temperature were investigated to identify successful operating conditions for SAS coprecipitation. Microparticles with a mean diameter ranging between 1.6 and 4.1 µm were successfully produced. Drug release analyses revealed that NIM dissolution rate from PVP/NIM microparticles was 2.5 times faster with respect to unprocessed drug. The possible precipitation mechanisms involved in the process were discussed.
Nano-carrier systems such as liposomes, polymersomes and micelles find applications in the delivery of a wide range of compounds including targeted delivery of pharmaceuticals. Nano-carrier systems have the ability to increase the bioavailability, reduce toxicity and avoid undesirable interactions of active pharmaceutical ingredients. In this work, a novel dense gas technique known as Depressurization of an Expanded Solution into Aqueous Media (DESAM) was used to produce different types of nano-carrier systems. The effects of using different types of dense gases and different operating temperatures were investigated. Encapsulation of hydrophilic compounds in the vesicles (liposomes and polymersomes) was also studied. The highest encapsulation efficiencies in liposomes and polymersomes achieved were 10.2% and 9.7%, respectively. The DESAM process was also able to reduce the residual solvent content in the product to 2.2% v/v, which is significantly lower than the solvent residual levels reported for conventional processing.
Full Article: http://pubs.acs.org/doi/abs/10.1021/la502594k
A modified supercritical antisolvent method, aiming at high yielding and high loading, is developed for preparation of drug-loaded polymeric nanoparticles. The modified method consists of three alternate stages: injecting solution via a nozzle into a precipitation vessel filled with supercritical CO2, static agitation, and washing of precipitated particles with supercritical CO2. The process stages are continuously repeated until ending injection of a desired amount of solution. The ultrasound operates during the entire process. Poly(lactic-co-glycolic acid) (PLGA) and curcumin are model components. The influences of the process parameters on the yielding and loading are investigated. The maximum yield of the curcumin–PLGA nanoparticles 50 nm in size and the curcumin loading in it reach 96% and 45%, respectively. High yield, high loading, and uniform size are attributed to the efficient mixing between solution droplets and antisolvent, and sequential washing using an antisolvent under ultrasonic agitation. Experimental data are fitted and optimized by neural network simulation.
This work reports experimental data of the solubility of b-carotene in pure acetone, ethyl acetate, ethanol and dichloromethane and in mixtures of these organic solvents in the temperature range of 10 to 60 °C under ambient pressure. The gravimetric method was employed to determine the solubility, using glass equilibrium cells. The results showed that the best solvents were those having solubility parameter values close to that of the solute. It was found that raising the temperature caused the solute solubility values for both pure and solvent mixtures to increase under all the experimental conditions. Moreover, no synergetic effects were observed on the solubility of b-carotene in solvent mixtures compared to pure solvents in the temperature range investigated. The UNIFAC model proved to be useful in predicting the solubility data.
Microparticles of theophylline were recrystallized using the high-pressure antisolvent technique. A mixture of ethanol and dichloromethane with a volumetric ratio of 1:1 was used as solvents, and compressed CO2 as antisolvent. The effects of process parameters (temperature, flow rate of solution and antisolvent, drying rate, initial solution concentration, diameter and length of the capillary expansion tube, and pressure gradient between the organic solution feed and the precipitation chamber) on particle size, size distribution and morphology were evaluated through an experimental design technique. In order to help selecting the appropriate operating conditions and understand the precipitation mechanism, the fluid phase behavior of ternary (CO2-solvents) and quaternary (CO2-solvents–theophylline) systems were investigated using a static synthetic method. Plate-like particles were produced in all experimental conditions with length ranging from 3 to 70 μm. Also, slightly agglomerated particles were produced in some experiments, while in others a quite pronounced agglomeration was observed. Phase diagram of the mixture revealed that the contact mechanism between solution and antisolvent occurred in two different ways, influencing the aggregation, particle size and particle size distribution. The X-ray powder diffraction patterns (XRD) showed a change in theophylline crystallinity. This fact was confirmed by differential scanning calorimetry (DSC) analysis. Also, infrared spectroscopy analysis (FTIR) showed that the recrystallized powder presented a degree of purity higher than that of unprocessed theophylline. Thermal gravimetric analysis (TGA) indicated that the lower mass loss temperature values were found for small size particles and particles with crystalline structure.
In this work, the coprecipitation of β-carotene and polyethylene glycol (PEG) is studied. First, the effect of pressure and temperature was studied (pressures of 8−12 MPa, temperatures of 288−313 K), Afterward, the effect of the initial concentration of the different substances on the morphologies of the particles was studied. X-ray diffraction (XRD), differential scanning calorimetry (DSC), and scanning electron microscopy (SEM) analysis were used to observe the nature of the particles that were obtained. The results indicated the sensitivity of the precipitation to temperature, making impossible to obtain particles at temperatures above 288 K. With regard to the concentration effect on the morphology of the particles, it was possible to obtain different morphologies just by changing the concentration ratio between the substances. Also, the analysis of the coprecipitates indicated that the β-carotene inside the polymer matrix must be in an amorphous form.
The objective of this work was to investigate the application of the solution enhanced dispersion by supercritical fluids (SEDS) technique for the precipitation of pure β-carotene and copolymer poly(3-hydroxybutirate-co-hydroxyvalerate) (PHBV), as well as some encapsulation tests of the solute in the biopolymer. The following parameters were investigated in the precipitation of pure β-carotene: pressure (8.0 and 12.0MPa), anti-solvent flow rate (20–40mL/min) and concentration of β-carotene in an organic dichloromethane solution (4 and 8mg/mL). For pure β-carotene, the results showed that the mean particle size varied from 3.8 to 246.8μm, depending on the processing conditions. The morphology of β-carotene was modified from plate-like to leaf-like particles, as verified by micrographs of scanning electronic microscopy (SEM). For the PHBV precipitation, the SEM micrographs showed that for all experimental conditions the morphology of polymer was different from the unprocessed material. The precipitated polymer presented a quasi-spherical shape with interconnected particles in the sub-micrometric range (particle size in the range of 278–570nm), while the unprocessed material was composed of films and large blocks. The co-precipitation tests showed that the best ratio of β-carotene to PHBV in solution was 1:3(w/w), which resulted in approximately 80% of encapsulation. Fluid phase behavior of the ternary systems CO2+dichloromethane+β-carotene and CO2+dichloromethane+PHBV was also investigated with the aim of elucidating the region of the phase diagram in which the precipitation occurs. Phase equilibrium data were measured in the temperature range of 303–343K, with CO2 compositions ranging from 40 to 90wt% for β-carotene, and from 30 to 90wt% for PHBV. Vapor–liquid and also solid–vapor–liquid phase transitions were observed in the phase equilibrium study. It was observed that the presence of β-carotene or PHBV in the ternary mixture had a little influence on the fluid phase behavior of the systems.
The supercritical antisolvent precipitation (SAS) process has been frequently applied to pharmaceutical compounds, due to its potential capacity to control particle size (PS) and distribution and the simple separation and recovery of the solvent and of the antisolvent. However until now, the SAS process has been performed prevalently in laboratory scale apparatus; therefore, process limitations that are significant on the large scale, have not been studied yet. These limitations may even lead to the failure of translating the process to commercial dimensions. Herein we report the results of SAS precipitation of Amoxicillin from N-methylpyrrolidone performed in a semi-continuous pilot plant equipped with a 5 dm3 precipitator, operated at 40°C and 150 bar. Non coalescing spherical microparticles were obtained with mode diameters ranging from 0.3 to 1.2 μm depending on the concentration of Amoxicillin in the liquid solution. The effect of the scale enlargement and of the kind of injection device on the powder size and morphology has been investigated and a comparison with laboratory scale results is also presented. The change of nozzle arrangement and diameter from the laboratory to the pilot scale does not affect significantly the PS and distribution of Amoxicillin.
The Solution-Enhanced Dispersion by Supercritical Fluids (SEDS) process is a promising technology for the production of ultrafine powders, composite microparticles, and other powders. Carotene/proanthocyanidin composite microparticles were obtained using supercritical CO2 (SC-CO2) as an antisolvent in a mixed solution of dichloromethane and ethanol. For the purpose of evaluating the efficiency of the supercritical fluid precipitation technologies in processing the composite microparticles and studying the effects of operating variables on the composite microparticle, the SEDS process through Prefilming Atomization (SEDS-PA) was used in this paper. Morphologies and particle sizes of the composite microparticles were analyzed by scanning electron microscopy and optical microscopy. The carotene concentrations in the composite microparticles were determined by spectrophotometry. The results show that the precipitates obtained under the experimental conditions are platelet-shaped carotene and proanthocyanidin composite microparticles with a mean particle size of 2−5 μm. The particle sizes of the composite microparticles increase as the temperature increases and decrease as the pressure and carotene concentration in the mixed solution each increase. The carotene concentration in the composite microparticles increases initially, then decreases with increasing temperature, and increases with increasing carotene concentration in the mixed solution, and no clear change dependence on pressure can be observed. The proanthocyanidins can effectively restrain the degradation of carotene in the composite microparticles.
Microparticles of poly(l-lactic acid) (PLLA), loaded with the antibiotic amoxicillin, have been produced with the SEDS (solution enhanced dispersion by supercritical fluid) process. Encapsulation of amoxicillin in PLLA was initially attempted from a suspension of amoxicillin microparticles in a solution of PLLA in dichloromethane (DCM). In addition, several mixtures of dichloromethane and dimethyl sulfoxide (DMSO), in which amoxicillin and PLLA were dissolved, were employed in an attempt to encapsulate the drug in the biodegradable matrix. The effect of process parameters such as pressure, temperature, concentration of solutes, and DCM/DMSO ratio on the encapsulation efficiency was investigated. In our study, high pressures and a coaxial nozzle for the introduction of the organic solution and the supercritical antisolvent were employed, resulting in the increased mixing of the two flows. An attempt was made to explain the different encapsulation percentages obtained at different operating conditions.
In view of developing new drug-delivery systems, microparticles of biocompatible polymer loaded with protein were produced using a supercritical antisolvent technique. As the polymer, poly(lactic acid) (PLA) of about 100 000 Da was used, whereas insulin was chosen as the protein model. To achieve microencapsulation, we started from a homogeneous solution of protein and polymer, to which the supercritical antisolvent is added; mixtures of dichloromethane and dimethyl sulfoxide were used to ensure the solubility of both the polymer and the protein. All experiments were performed in semicontinuous mode. A preliminary study with PLA alone was done in order to select the best operative condition and to control the particle dimension and their diameter distribution range, especially with mixtures of the two solvents. Then, the microspheres of PLA charged with insulin were produced; the average diameters ranged from 0.5 to 2 μm. The composition of these particles was determined analytically, and the protein bioactivity was checked.
Solids precipitation from liquid solvents, with dissolution by high-pressure CO2 as an antisolvent to create supersaturation, is a potentially attractive crystallization process. Solids can be recrystallized and easily isolated from the liquid solvent. The gas antisolvent solvent (GAS) process was used to separate and purify β-carotene from a mixture containing carotene oxidation products. Total β-carotene was successfully separated from oxides, and an enriched traras-β-carotene was obtained from its cis isomers. The separation was carried out in both batch and continuous modes. Relative solubility of the analytes and the antisolvent (CO2) have a dramatic influence on the absolute yield and purity of the product.
This work investigates the application of the Solution-Enhanced Dispersion by supercritical fluids technique for the precipitation of β-carotene. The effect of pressure (8.0–12.0 MPa), temperature (293–313 K) anti-solvent flow rate (20–40 mL/min), solution flow rate (1–4 mL/min) and concentration of β-carotene in the dichloromethane solution (4 and 8 mg/mL) on the precipitation yield, particle morphology and particle size and size distribution was examined. Precipitated powders presented mean particle size varying from 3.2 μm to 96.8 μm with morphology of β-carotene microparticles changing from plate-like to leaf-like particles. The statistical analysis of the experimental results revealed that pressure, organic solution concentration and CO2 flow rate had a significant effect on particle size. The precipitation yield was observed to be within the range of 71–94% and was statistically influenced by system temperature and pressure, and anti-solvent flow rate.