Particles From Gas Saturated Solutions Research Articles

Green Processing of Black Raspberry Pomace: Application of Sonotrode-Based Extraction Technique and Particles from Gas-Saturated Solutions (PGSS) Technology.

The aim of this study was to develop, for the first time, anthocyanin-enriched fractions from black raspberry pomace (BRP) using ultrasound-assisted extraction (UAE) via sonotrode and the Particles from Gas-Saturated Solutions (PGSS) process. UAEs with different amplitudes and sonication times were evaluated and showed relevant effects on the yields of target analytes. The raspberry pomace extracts were formulated in a powder form by PGSS using glyceryl monostearate as a carrier at different extract-to-carrier ratios of 1:11, 1:5, and 1:3. The effects of all variables were evaluated in terms of extraction yield, total phenolic content, and encapsulation yield. UAE was strongly affected by amplitude, and the highest amplitude (100%) provided the best results for extraction yield and total phenolics. HPLC of UAE extracts and powders was utilized for quantification of polyphenol compounds, showing cyanidin-3-rutinoside as a main compound, followed by cyanidin-3-glucoside, rutin, ellagic acid, and gallic acid. These results show that these time-efficient and high-performance techniques enable the production of natural fractions from industrial BRP with acceptable characteristics to be used for the development of nutraceuticals and different food formulations.

Comparative Study of Cinnamon and Paprika Oleoresins Encapsulated by Spray Chilling and Particles from Gas Saturated Solutions Techniques: Evaluation of Physical Characteristics and Oleoresins Release in Food Simulated Media

In this study, cinnamon and paprika oleoresins were encapsulated by two technologies, respectively, spray chilling and particles from gas saturated solutions. Both technologies used palm oil as wall materials. The physical characteristics of the microparticles were compared as well as the oleoresins release behavior in high- and low-fat simulated food media. The spray chilling microparticles had an average diameter of 143.7 ± 1.5 µm, spherical shape, smooth surface, and passable flow property. In contrast, microparticles obtained by particles from gas saturated solutions (PGSS) showed an average diameter of 105.7 ± 0.6 µm, irregular shape, porous surface, poor flow property but higher encapsulation efficiency. In evaluating the compounds released in a simulated food medium, the spray chilling particles delivered 30.7%, while PGSS reached 23.1% after 1 h. Both microparticles well fitted the Kosmeyer-Peppas (R2 = 0.98 and 0.96 for spray chilling and PGSS) and Peppas-Sahlin models (R2 = 0.98 and 0.97 for spray chilling and PGSS). However, spray chilling microparticles showed a diffusion mechanism, while for PGSS ones erosion was the main mechanism. Despite the different physical characteristics, both microparticles proved to be possible facilitators in delivering oleoresins in food products.

Microencapsulation of linseed oil enriched with carrot pomace extracts using Particles from Gas Saturated Solutions (PGSS) process

This work aimed to evaluate the oxidative stability of linseed oil microcapsules formulated with carrot pomace extract (CPE). CPE, obtained with supercritical carbon dioxide technique carried out at 30 MPa, 60 °C for 120 min with CO2 flow rate of 2 L/h using ethanol as co-solvent (14%, w/w), was mixed with linseed oil at different concentrations (0.8–16 mg/g of oil) and sunflower wax as wall material. Microcapsules were obtained by PGSS performed at 75 °C for 30 min, 10, 20 and 30 MPa. The best encapsulation efficiency, powder density and flowability were achieved by applying PGSS at 10 MPa. These samples also showed the highest oxidative stability (28 ± 2 h), which was furthermore improved up to 43 ± 2 h with the addition of CPE (16 mg/g of oil).

Encapsulation of Lactoferrin for Sustained Release Using Particles from Gas-Saturated Solutions

The particles from gas saturated solutions (PGSS) process were performed to encapsulate lactofer-rin, an iron-binding milk glycoprotein, using supercritical carbon dioxide (scCO2). A natural en-teric polymer, shellac, was used as a coating material of lactoferrin carried out by the PGSS pro-cess. Conditions were optimized by applying different temperatures (20–50 °C) and pressures (8–10 MPa) and the particles were evaluated for particle shape and size, lactoferrin encapsulation ef-ficiency, Fourier transform infrared (FTIR) spectroscopy to confirm lactoferrin entrapment and in vitro dissolution studies at different pH values. Particles with an average diameter of 75.5 ± 7 μm were produced with encapsulation efficiency up to 71 ± 2%. Furthermore, particles that showed high stability in low pH (pH 1.2) and a sustained release over time (t2h = 75%) in higher pH (pH 7.4) suggested an effective encapsulation process for the protection of lactoferrin from gastric di-gestion.

Development of Components of Prolonged Action Antibacterial Dosage Forms Using SCF Technologies

Gentamicin and levofloxacin are encapsulated into bioresorbable polymer scaffolds and microparticles by the SCF methods: particles from gas saturated solutions (PGSS) and plasticization, with the subsequent foaming of amorphous polymers using supercritical carbon dioxide. The kinetics of the release of the incorporated drug substances into model physiological media are studied. It is shown that the use of the developed methods of SCF-encapsulation of drugs in bioresorbable carriers allows varying the size, shape, and morphology of the formed structures and, accordingly, the rate of release of the drugs into the physiological environments. In our opinion, this approach can be very promising for the development of components of new highly effective antibacterial prolonged action dosage forms.

Formation of edible oil-loaded beeswax microparticles using PGSS – Particles from Gas-Saturated Solutions

This research aimed to study the formation of edible oil-loaded beeswax microparticles using the Particles from Gas-Saturated Solutions (PGSS) process. Lipid binary mixtures (1:1 w/w) of beeswax with avocado oil or Brazil nut oil were studied as models. The PGSS process consisted of contacting the lipid binary mixture with supercritical CO2 in an autoclave at pressures from 150 to 300 bar at a temperature of 60 °C with an agitation at 1250 rpm for 1 h and the subsequent expansion of the solution (lipids + CO2) through a nozzle of 203.2 μm. The resulting edible oil-loaded beeswax microparticles had a sponge-like morphology and sizes of 162−180 μm and 96−128 μm when formulated with avocado oil and Brazil nut oil, respectively. Crystallinity and internal physical structure of the particles suggested uniform incorporation of edible oils into the crystalline lattice of beeswax. These particles could formulate ingredients for functional food products.

Microencapsulation of drug with enteric polymer Eudragit L100 for controlled release using the particles from gas saturated solutions (PGSS) process

The objective of this study is to evaluate the solubility of an enteric polymer, Eudragit L100, in a supercritical CO2-ethanol mixture, and to produce spherical microcapsules for phenylalanine using Eudragit L100 as the coating substance by the PGSS process both at temperature 50 °C and pressures from 8 to 12 MPa. The average particle size obtained from the particles from gas saturated solution (PGSS) process decreased from 200.9 μm ± 20.5 μm to 140.6 μm ± 40.1 μm with increasing pressure from 8 to 12 MPa. The highest encapsulation efficiency of 68 ± 7% was obtained from the microcapsules produced from PGSS conducted at 50 ℃ and 10 MPa which SEM observation confirmed spherical microcapsules without aggregation. Sustained drug release assay of the microcapsules showed a sustained and enhanced drug release at low and high pH conditions, respectively, indicating successful micro coating of phenylalanine by Eudragit L100.

Lidocaine-Loaded Solid Lipid Microparticles (SLMPs) Produced from Gas-Saturated Solutions for Wound Applications.

The delivery of bioactive agents using active wound dressings for the management of pain and infections offers improved performances in the treatment of wound complications. In this work, solid lipid microparticles (SLMPs) loaded with lidocaine hydrochloride (LID) were processed and the formulation was evaluated regarding its ability to deliver the drug at the wound site and through the skin barrier. The SLMPs of glyceryl monostearate (GMS) were prepared with different LID contents (0, 1, 2, 4, and 10 wt.%) using the solvent-free and one-step PGSS (Particles from Gas-Saturated Solutions) technique. PGSS exploits the use of supercritical CO2 (scCO2) as a plasticizer for lipids and as pressurizing agent for the atomization of particles. The SLMPs were characterized in terms of shape, size, and morphology (SEM), physicochemical properties (ATR-IR, XRD), and drug content and release behavior. An in vitro test for the evaluation of the influence of the wound environment on the LID release rate from SLMPs was studied using different bioengineered human skin substitutes obtained by 3D-bioprinting. Finally, the antimicrobial activity of the SLMPs was evaluated against three relevant bacteria in wound infections (Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa). SLMPs processed with 10 wt.% of LID showed a remarkable performance to provide effective doses for pain relief and preventive infection effects.

Supercritical fluid technology for solubilization of poorly water soluble drugs via micro- and naonosized particle generation.

Approximately two-third of the compounds in the pharmaceutical industry were developed through combinatorial chemistry and high throughput screening of particulate solids. Poor solubility and bioavailability of these pharmaceuticals are challenging attributes confronted by a formulator during product development. Hence, substantial efforts have been directed into the research on particle generation techniques. Although the conventional methods, such as crushing or milling and crystallization or precipitation, are still used; supercritical fluid technology introduced in the mid-1980s presents a new method of particle generation. Supercritical fluid processes not only produce micro- and nanoparticles with a narrow size distribution, they are also employed for the microencapsulation, cocrystallization, and surface coating with polymer. Recognized as a green technology, it has emerged as successful variants chiefly as Rapid Expansion of supercritical solutions (RESS), Supercritical anti-solvent (SAS) and Particles from Gas Saturated Solution (PGSS) depending upon type of solvent, solute, antisolvent and nebulization techniques. Being economical and eco-friendly, supercritical fluid technolgy has garnered considerable interest both in academia and industry for modification of physicochemical properties such as particle size, shape, density and ultimately solubility. The current manuscript is a comprehensive update on different supercritical fluid processes used for particle generation with the purpose of solubility enhancement of drugs and hence bioavailability.

CO2-assisted production of polyethylene glycol / lauric acid microparticles for extended release of Citrus aurantifolia essential oil

Applications of essential oils as chemotherapeutics are limited because these aromatic oils are generally volatile, insoluble in aqueous media and easily degraded to non-active constituents when subjected to thermal-oxidative processes. The particles from gas-saturated solution (PGSS) technology allows for non-destructive processing of volatile oils into micronized formulations under high pressure and moderate temperature using supercritical carbon dioxide (scCO2). In this study, essential oil from lime (Citrus aurantifolia) with proven antidiabetic activity was processed with polyethylene glycol (PEG) and lauric acid (LA) using scCO2 in a high pressure reactor for 2 h at 120 bar and 45 °C. The polymer-oil mixtures were co-precipitated and micronized through a 500 μm nozzle. PGSS processing of C. aurantifolia oil with PEG and LA yielded roughly spherical microparticles with sizes ∼ 2 μm. Inclusion of the LA and encapsulation of the limonene-rich oil into the PEG particles were confirmed using FTIR and GC/MS respectively. Melting point and heat of fusion of the PEG/LA microparticles were lower when compared with particles produced with PEG only, resulting in higher oil loading capacity and yield. The scCO2-assisted polymeric encapsulation of the volatile oil reduced rapid vaporization and incorporation of LA with the PEG-oil formulation extended the mean release time in simulated physiological solutions. Free radical scavenging and alpha-amylase inhibitory activities of the lime oil were also preserved following encapsulation in the PEG/LA microparticles. In summary, production of PEG/LA microparticles with high yield and loading capacity of bioactive lime essential oil was achieved using the scCO2 encapsulation technology.

Paramagnetic bioactives encapsulated in poly(D,L-lactide) microparticules: Spatial distribution and in vitro release kinetics

Poly(D,L-lactide) microparticles impregnated with a number of bioactive paramagnetic compounds have been fabricated using two SCF techniques: 1). PGSS (Particles from Gas Saturated Solution) and 2). polymer plasticization and swelling by supercritical carbon dioxide followed by its cryomilling. Electron paramagnetic resonance (EPR) spectroscopy manifested homogeneous spatial distribution for the most of these substances encapsulated into the polymer. Irreversible relaxation processes in the prepared polymer structures and formulations were not observed. The qualitative difference in the release kinetics of paramagnetic molecules of different structure from the polymer microparticles into the phosphate-buffered saline (PBS, pH = 7.4) was demonstrated. pH-sensitive ATI spin probe proved the decrease (up to ≤ 4.5) of local pH inside the microparticles during the first 9 days after its immersion in PBS.

Characterization and pharmacokinetic evaluation of microcomposite particles of alpha lipoic acid/hydrogenated colza oil obtained in supercritical carbon dioxide

The work reported here is an extension of our previous findings in which supercritical composite particles (SCP) of alpha lipoic acid (ALA) masked with hydrogenated colza oil (HCO) named as ALA/HCO/SCP were obtained by the modified particles from gas-saturated solutions (PGSS) process in supercritical carbon dioxide in order to obscure the unpleasant taste and odor of ALA. The masking effect on ALA/HCO/SCP was compared with the widely used mechano-chemically masked formulation of ALA and HCO named as MC-50F. In the present study, ALA/HCO/SCP particles were found to have a significant improvement in regard to bitterness, numbness, and smell compared to ALA bulk powders suggesting they were well coated. The pharmacokinetic parameters for ALA/HCO/SCP and ALA bulk powder gave similar values but were significantly different from those of MC-50F. The amount of ALA absorbed into the body, in the administered ALA/HCO/SCP, was comparable to that absorbed by ALA bulk powder, whereas about half portion of ALA of the MC-50F was not absorbed, because the ALA/HCO/SCP particles were small enough and the particles of MC-50F were relatively large and had smaller specific surface area. Therefore, this study suggested a newly masked candidate may offer functional particles with maintained efficacy.

Microencapsulation and Nanoencapsulation Using Supercritical Fluid (SCF) Techniques.

The unique properties of supercritical fluids, in particular supercritical carbon dioxide (CO2), provide numerous opportunities for the development of processes for pharmaceutical applications. One of the potential applications for pharmaceuticals includes microencapsulation and nanoencapsulation for drug delivery purposes. Supercritical CO2 processes allow the design and control of particle size, as well as drug loading by utilizing the tunable properties of supercritical CO2 at different operating conditions (flow ratio, temperature, pressures, etc.). This review aims to provide a comprehensive overview of the processes and techniques using supercritical fluid processing based on the supercritical properties, the role of supercritical carbon dioxide during the process, and the mechanism of formulation production for each process discussed. The considerations for equipment configurations to achieve the various processes described and the mechanisms behind the representative processes such as RESS (rapid expansion of supercritical solutions), SAS (supercritical antisolvent), SFEE (supercritical fluid extraction of emulsions), PGSS (particles from gas-saturated solutions), drying, and polymer foaming will be explained via schematic representation. More recent developments such as fluidized bed coating using supercritical CO2 as the fluidizing and drying medium, the supercritical CO2 spray drying of aqueous solutions, as well as the production of microporous drug releasing devices via foaming, will be highlighted in this review. Development and strategies to control and optimize the particle morphology, drug loading, and yield from the major processes will also be discussed.

Omega–3 encapsulation by PGSS-drying and conventional drying methods. Particle characterization and oxidative stability

Particles from Gas-Saturated Solutions (PGSS)-drying has been used as a green alternative to encapsulate omega–3 polyunsaturated fatty acids (n–3 PUFAs) at mild, non-oxidative conditions. PGSS-dried particles have been compared to those obtained by conventional drying methods such as spray-drying and freeze-drying, finding encapsulation efficiencies (EE) up to 98% and spherical morphology for PGSS- and spray-dried particles. Freeze-dried powders showed irregular morphology and EE from 95.8 to 98.6%, depending on the freezing method. Differential scanning calorimetry (DSC) analysis revealed glass-transition and melting peaks of OSA-starch and a cold-crystallization peak corresponding to the encapsulated n–3 PUFA concentrate. Compared to conventionally dried powders, PGSS-dried microparticles showed lower primary and secondary oxidation after 28 days of storage at 4 °C. Ascorbic acid addition combined with the mild processing conditions of PGSS-drying yielded particles with a maximum peroxide value of 2.5 meq O2/kg oil after 28 days of storage at 4 °C.

Fucoxanthin-rich oil encapsulation using biodegradable polyethylene glycol and particles from gas-saturated solutions technique

Fucoxanthin is a precious marine carotenoid with multiple bioactivities such as antioxidant, anti-obesity, and anti-cancer effects. Despite its valuable properties, fucoxanthin possesses high sensitivity when exposed to aerial, thermal, or light factors. Our study aims to extract fucoxanthin-rich oil (FO) from Saccharina japonica using supercritical carbon dioxide with sunflower oil (SFO) as co-solvent and encapsulate the extracted oil using particles from gas-saturated solutions (PGSS) process with polyethylene glycol (PEG) as a biodegradable coating. The encapsulation efficiency (EE) of the extracted oil based on fucoxanthin content was optimized using response surface methodology with Box-Behnken design (BBD). Three independent factors, including mixing ratio of FO and PEG, temperature, and pressure, were optimized. The encapsulated particles (EP) at optimized conditions were characterized for their powder properties and storage stability. FO and EP were measured in antioxidant activities and fatty acids content. The optimum EE was approximately 82%, implying the capability of PGSS and PEG in encapsulating nutritious oil.

Microencapsulation of omega-3 polyunsaturated fatty acids and astaxanthin-rich salmon oil using particles from gas saturated solutions (PGSS) process

Salmon oil rich in omega-3 polyunsaturated fatty acids and astaxanthin was microencapsulated in polyethylene glycol-6000 using particles from gas saturated solutions process. The process conditions viz. temperature (45–55 °C), pressure (15–25 MPa), oil and polymer ratio (1:2.5–1:10), and nozzle size (300–500 μm) were optimized for maximizing encapsulation efficiency. The maximum encapsulation yield of 79.20% was obtained in the microparticle produced at a temperature of 50 °C, pressure of 25 MPa, oil and polymer ratio of 1:5, and nozzle diameter of 400 μm. Astaxanthin content of 40.60 μg/g oil in microparticle; bulk density of 0.26%; cohesiveness and flowability measured by the Carr index of 12.76, and wettability of 5.91 min of the microparticles were found. Scanning electron microscopic analysis showed microparticles of different morphologies, from spherical or elongated to amorphous-shaped, with the size of the microparticles between 0.37 μm and 449 μm. Fourier transform infra-red spectroscopy spectra and fatty acid compositions of salmon oil before and after microparticle formation suggested that there was no remarkable alteration due to the PGSS process. Microparticles showed significant thermogravimetric stability up to 350 °C, and in vitro release of oil in fluids stimulating gastric conditions was faster than in distilled water.

Formation, characterization and release behavior of citrus oil-polymer microparticles using particles from gas saturated solutions (PGSS) process

Citrus oil was encapsulated in polyethylene glycol (PEG) using the particles from gas saturated solutions (PGSS) technique. The impact of process conditions, i.e., pressure, temperature, and citrus oil/PEG mixing ratio on the characteristics of formed microparticles has been investigated. The particles with sizes of 190.56–373.32μm and different shapes were obtained. The efficiency of encapsulation ranged between 43.95% and 83.87%. The oxidative stability and in vitro release was significantly changed depending on storage temperature and pH of the incubation medium, respectively, and the oxidative stability was significantly improved by encapsulation using PGSS process.

Polymorphism of Risperidone in Supercritical Fluid Processes of Micronization and Encapsulation into Aliphatic Polyesters

The specific features of the transformation of risperidone polymorphs as a result of micronization and encapsulation into aliphatic polyesters (polylactides and polylactoglycolide) have been studied using supercritical (SC) carbon dioxide. It has been shown that the micronization of risperidone, which originally is polymorph A, via the rapid expansion of supercritical solutions (RESS) and the supercritical antisolvent (SAS) precipitation leads to its crystallization in less thermodynamically stable polymorph B. This transition is complete for SAS and only partial for RESS. When these micronized samples are encapsulated into polylactides and polylactoglycolides via the formation of particles from gas-saturated solutions (PGSS) and monolithization with further cryogrinding (MCG), risperidone polymorph B is partially converted back into polymorph A. At the same time, the micronization of initial risperidone polymorph A via cryogrinding and its further PGSS and MCG encapsulation into polylactides or polylactoglycolides does not result in any change in the polymorphic state of risperidone, and it always remains in initial polymorph A.

Polymorphic transition of lipid particles obtained with the PGSS process for pharmaceutical applications

The bioavailability of a pharmaceutical depends on the crystal structure of a polymorphic active ingredient or excipient. By changing the process parameters of the PGSS (Particles from Gas Saturated Solutions) process i.e. thermodynamic conditions of the solidification process it is possible to vary the crystal modification of polymorphic products. In a series of PGSS experiments microparticles of the polymorphic excipient tristearin as well as of mixtures of tristearin and the emulsifier sorbitan monolaurate were successfully produced. Pre-expansion pressure was varied between 6 and 22MPa. The effects of process dependent parameters on the crystallization were investigated via scanning electron microscopy, differential scanning calorimetry and X-ray powder diffraction.Metastable α-forms of tristearin were found immediately after the processing for all experiments. Further it was found that it is possible to shift the conversion rate of polymorphic transitions in the product either by varying the process parameters or by adding the emulsifier.

Production of encapsulated quercetin particles using supercritical fluid technologies

Quercetin is an antioxidant compound with highly promising pharmacological properties against a wide variety of diseases. A major limitation for the clinical application of quercetin is its low bioavailability, due to its low solubility in water. In this work, quercetin is microencapsulated in a surfactant material with the objective of increasing its bioavailability. For this, quercetin is first treated using Supercritical Fluid Extraction of Emulsions in order to precipitate it in nanometric scale in an aqueous suspension, and then this suspension is further treated by Particles from Gas Saturated Solutions (PGSS)-drying technology, to obtain quercetin loaded dried particles in micrometric scale. Soy-bean lecithin and Pluronic L64® are used as surfactant and encapsulating materials. Mircoencapsulation of quercetin by lyophilisation of SFEE-produced aqueous suspensions is also studied in order to compare it with the results of PGSS-drying. Samples are characterized considering encapsulation efficiency, antioxidant activity and Franz-cell measurements of transdermal diffusion of encapsulated quercetin product as assessment of its bioavailability. It is observed that samples encapsulated by SFEE and PGSS-drying are more homogeneous and less crystalline than samples obtained by lyophilisation, which results in a higher transdermal diffusivity.