External Gelation Research Articles

Formulation and In Vitro Evaluation of Taste- Masked Prednisolone Orodispersible Tablets

Background: prednisolone is a corticosteroid with a very bitter taste acts as anti- anti-inflammatory and immune suppressant drug and it is used at any age. Objective: To improve patient compliance by masking the bitter taste of the drug to be delivered as an orodispersible tablet. Methods: External ionic gelation using sodium alginate (0.5%w/v) and calcium chloride (1% w/v) in presence of 0.5% w/v carbopol 940 was used to prepare taste masked beads loaded with prednisolone to be compressed as orodispersible tablets. Results: The bitter taste of was masked by preparing beads composed of 1:1:1 (sodium alginate: Carbopol 940: prednisolone) which released only 0.77 % of the drug in pH 6.8 (pH of oral cavity). The ODT prepared by direct compression using taste masked beads equivalent to 5 mg PRD, 3% crospovidone, 2% PVP, 1% talc, 1% magnesium stearate and combination of Avcil® PH 102 and mannitol at (1:1) ratio was the optimum formula (T6) with hardness of 3.9± 0.32 kg, , friability 0.45%, thickness 2.5 ± 0.05 mm, % drug content 98.2% ± 1.8, wetting time 18.7 ± 1.3 sec, water absorption 41 ± 2.1%, disintegration time 15.3 ± 0.5 sec. and released only 0.75% ± 0.01 of PRD in an oral pH of 6.8 within one minute (indicating good taste masking). Its release in the stomach (pH 0.1N HCl) and intestine (pH 6.8) was continued for up to two hours. Conclusion: it can be concluded that the external ionic gelation method successfully masked the bitter taste of prednisolone and can also be formulated as taste-masked orodispersible tablets by the direct compression method. Received: Jan. 2023 Accepted: May 2023 Published: Oct.2023

Realizing Eco-Friendly Water-Resistant Sodium-Alginate-Based Films Blended with a Polyphenolic Aqueous Extract from Grape Pomace Waste for Potential Food Packaging Applications.

Water-resistant and environmentally friendly sodium-alginate-based films have been investigated to develop functional materials to extend the food's shelf-life. A water-stable alginate-based film was prepared, employing both the internal and external gelation approach in the presence of CaCl2. To apply this film to food packaging and thus preserve food quality, the aim of this work is to perform a chemical and physical characterization of the proposed materials, evidencing the main features and stability under different work conditions. Water contact angle measurements showed a value of 65°, suggesting an important reduced hydrophilic character of the obtained alginate films due to the novel CaCl2-induced compacted polymer network. The film's stability was thus checked through swelling measurements in water after varying pH, temperature, and ionic strength. The film was stable at high temperatures and not pH-responsive. Only highly concentrated salt-based solutions negatively affected the proposed packaging, causing a large swelling. Furthermore, a water-based polyphenolic extract from grape (Vitis vinifera L.) pomace waste was embedded inside the films in different amounts in order to confer additional properties. The extract's polyphenolic content (evaluated from HPLC/MS-MS measurements) endowed the films' UV-light screening and enhanced antioxidant properties. These important findings suggest the additional potential role of these films in protecting food from light deterioration. The stability of these hybrid films was also checked by observation, as the polyphenols' presence did not largely alter the alginate network that occurred yet was water-resistant under the described work conditions.

Calcium silicate‐reinforced pH‐sensitive alginate‐gellan gum composite hydrogels for prolonged drug delivery

AbstractThis study disclosed the synthesis and characterization of externally and/or internally crosslinked alginate‐gellan gum composite interpenetrating polymer networks (IPN) and IPN hydrogel microspheres for controlled delivery of gliclazid. The internal cross‐linking of the polymer sol was accomplished via slow release of Ca2+ ions from calcium silicate in presence of gluconic acid d‐lactone. The microspheres had spherical shape with smooth surface morphology. The IPN or composite IPN hydrogel microspheres had drug entrapment efficiency of 70%–76%. Incorporation of gellan gum or gellan gum/calcium silicate in the alginate sol sustained the release of drug in simulated gastrointestinal fluids over 12 h without any sign of particle disintegration. Inclusion of calcium silicate in alginate gels was ineffective in controlling drug release under simulated gastrointestinal milieu. The drug release obeyed anomalous diffusion mechanism after inclusion of gellan gum or gellan gum‐calcium silicate in the alginate gel microspheres. Fourier‐transform infrared (FTIR) spectroscopy and zeta analysis confirmed absence of drug‐polymer chemical interaction. The thermal and x‐ray diffraction analyses suggested that the drug transformed into amorphous state after incorporation into composite hydrogel system. Hence, it may be advantageous to combine internal and external gelation procedures for creating composite IPN or IPN hydrogel microspheres for avoiding burst effect of alginate microspheres and managing desired drug release patterns in vitro.

Alginate microcapsules produced by external gelation in milk with application in dairy products

Alginate microcapsules produced by external gelation in milk with application in dairy products

Speciation and Ammonia-Induced Precipitation of Neptunium and Uranium Ions.

The pH evolution and corresponding changes in the UV-Vis-NIR absorption spectra of oxygenated neptunium (NpO2+ and NpO22+) and uranyl ions (UO22+) in nitric acid are investigated during titration with an aqueous NH3 solution. The speciation and precipitation regimes between acidic (pH 1.5) and alkaline (pH 10) conditions at room temperature are discussed to assess the suitability of Np(V) or Np(VI) in sol-gel conversion processes for fuel target fabrication. Under the applied experimental conditions, Np(V) hydrolyzes and precipitates into the insoluble hydroxide NpO2OH only above pH values 7.5 and an increase up to pH 10.0 is required to precipitate quantitatively. Np(VI) displays changes in the coordination environment of NpO22+ ions in the pH interval 1.6-4.0, similar to what is observed for U(VI). Precipitation into NpO3·H2O or other hydroxide compounds takes place between pH 4.0 and 5.9, which overlaps largely with precipitation of ammonium diuranate species from the U(VI) solution. The use of concentrated NH3 aqueous solution, as commonly used in the external gelation process, will allow to quantitatively precipitate both Np(V) and Np(VI) species. Internal gelation process conditions, on the other hand, seem incompatible with the high pH required to precipitate Np(V) completely. For fabricating mixed-oxide (U,Np) targets using sol-gel conversion, a feed broth containing Np(VI) and U(VI) will be required to achieve homogeneous gelation.

Internally crosslinked alginate-based bioinks for the fabrication of in vitro hepatic tissue models

Bioprinting is a key technique to fabricate cell-laden volumetric constructs with controlled geometry. It can be used not only to replicate the architecture of a target organ but also to produce shapes that allow for the mimicry, in vitro, of specific desired features. Among the various materials suitable to be processed with this technique, sodium alginate is currently considered one of the most appealing because of its versatility. To date, the most widespread strategies to print alginate-based bioinks exploit external gelation as a primary process, by directly extruding the hydrogel-precursor solution into a crosslinking bath or within a sacrificial crosslinking hydrogel, where the gelation takes place. In this work, we describe the print optimization and the processing of Hep3Gel: an internally crosslinked alginate and ECM-based bioink for the production of volumetric hepatic tissue models. We adopted an unconventional strategy, by moving from the reproduction of the geometry and the architecture of liver tissue to the use of bioprinting to fabricate structures that can promote a high degree of oxygenation, as is the case with hepatic tissue. To this end, the design of structures was optimized by employing computational methods. The printability of the bioink was then studied and optimized through a combination of different a priori and a posteriori analyses. We produced 14-layered constructs, thus highlighting the possibility to exploit internal gelation alone to directly print self-standing structures with finely controlled viscoelastic properties. Constructs loaded with HepG2 cells were successfully printed and cultured in static conditions for up to 12 d, underlining the suitability of Hep3Gel to support mid/long-term cultures.

Encapsulation of Carvacrol-Loaded Nanoemulsion Obtained Using Phase Inversion Composition Method in Alginate Beads and Polysaccharide-Coated Alginate Beads.

Nanoemulsions have been widely studied as lipophilic compound loading systems. A low-energy emulsification method, phase inversion composition (PIC), was used to prepare oil-in-water nanoemulsions in a carvacrol-coconut oil/Tween 80®-(linoleic acid-potassium linoleate)/water system. The phase behaviour of several emulsification paths was studied and related to the composition range in which small-sized stable nanoemulsions could be obtained. An experimental design was carried out to determine the best formulation in terms of size and stability. Nanoemulsions with a very small mean droplet diameter (16-20 nm) were obtained and successfully encapsulated to add carvacrol to foods as a natural antimicrobial and antioxidant agent. They were encapsulated into alginate beads by external gelation. In order to improve the carvacrol kinetics release, the beads were coated with two different biopolymers: chitosan and pullulan. All formulations were analysed with scanning electron microscopy to investigate the surface morphology. The release patterns at different pHs were evaluated. Different kinetics release models were fitted in order to study the release mechanisms affecting each formulation. Chitosan-coated beads avoided the initial release burst effect, improving the beads' structure and producing a Fickian release. At basic pH, the chitosan-coated beads collapsed and the pullulan-coated beads moderately improved the release pattern of the alginate beads. For acid and neutral pHs, the chitosan-coated beads presented more sustained release patterns.

Advanced insight on the water dynamics of anisotropic hydrogels by field-cycling nuclear magnetic resonance: Application of 3-Tau model

Fast field cycling (FFC) nuclear magnetic resonance (NMR) relaxometry is used to investigate an anisotropic polygalacturonate hydrogel formed by the diffusion of calcium ions from an external reservoir (external gelation). Such a hydrogel has a gradient of polymer density accompanied by a gradient of the mesh size of its 3D network. The NMR relaxation process is dominated by the interaction of proton spins between water molecules located at polymer interfaces and in nanoporous spaces. The FFC NMR experiment provides the spin-lattice relaxation rate R1ω as a function of Larmor frequency ω producing dispersion (NMRD) curves that are highly sensitive to the dynamics of the protons at the surfaces. The hydrogel is sliced into three parts and the NMR profile for each hydrogel slice is measured. The NMRD data for each slice is interpreted using the 3-Tau Model with the aid of user-friendly fitting software called 3TM. The key fit parameters include three nano-dynamical time constants and the average “mesh size” which collectively determine the bulk water and water surface layer contribution to the total relaxation rate. The results are consistent with independent studies where comparison is possible.

Internal gelation of alginate microparticle prepared by emulsification and microfluidic method: Effect of Ca-EDTA as a calcium source

Alginate microparticles were prepared by emulsification/internal gelation and microfluidic/internal gelation technique. Calcium-ethylenediaminetetraacetic acid (Ca-EDTA) was used as a calcium source, which could release Ca2+ ions to crosslink with the alginate chain by adding acid. Effects of emulsification speed, Ca-EDTA concentration, and crosslinking time on morphology, mechanical properties, rheological properties were investigated. A high-speed homogenizer was used to reduce the W/O emulsion size in the emulsification method. The smooth surface morphology of alginate particles was found from internal gelation while particles from external gelation showed a rough surface. Mechanical and rheological measurements demonstrated that a higher Ca2+ provided denser particles. The crosslinking time played a significant role in rheological properties. Double-gelation which was internal gelation followed by external gelation resulted in even higher stiffness compared with the particles from only internal crosslinking. Using the microfluidics technique, we could generate monodisperse alginate particles with more uniformity and controllable size. Thus, alginate particles can be fabricated using a continuous process which can avoid batch-to-batch variation.

Environmentally friendly starch/alginate aerogels for copper adsorption from aqueous media. A microstructural and kinetic study

This work investigated the synthesis and characterization of alginate/starch porous materials and their application as copper ions adsorbents from aqueous media. Initially, pregel aqueous solutions with different biopolymer concentrations (1, 3, and 5% w/w) and alginate contents (25, 50, and 75% w/w) were prepared. Hydrogel formation was performed by internal and external gelation methods. Finally, the drying step was done via CO2 sc leading to aerogels and via freeze-drying leading to cryogels. Process parameters influence on the final properties of materials was evaluated by BET isotherms, SEM, EDS, and TGA. Regardless the gelation method applied, interesting materials with meso- and macro-pore structure were prepared from pregel mixtures with 3% w/w biopolymer concentration and an alginate content of only 25% w/w. Low alginate content reduces the final cost of the materials. Concerning copper removal, the adsorption data were well fitted to the pseudo-second order kinetic model for aerogels and cryogels, showing aerogels the highest adsorption capacity (40 mg/g) and removal efficiency (∼ 92%). Materials demonstrated excellent reusability throughout five consecutive adsorption/desorption cycles. Hence, environmentally friendly materials with a high practical value as low-cost bioadsorbents were synthesized, having great performance in the removal of copper ions from aqueous solution.

Fabrication of crack-free oxidic thorium–cerium microspheres by an external gelation process

Thorium dioxide as an excellent matrix with stable properties is available for the direct incineration of plutonium, while (Th,Pu)O2 is a promising advanced fuel, which can be applied to a wide range of reactor types. In this study, cerium was used to simulate plutonium owing to their similar physicochemical properties. (Th1-xCex)O2 kernels were prepared by an external gelation process, which employs thorium and ceric ammonium nitrate as source materials, ammonium hydroxide as a neutralizing agent, polyvinyl alcohol as a thickening agent, and an ammonia gas ring for preliminary forming. The effect of the reaction temperature, reactant concentration, and pH on the feeding solution gelation properties was investigated. After the dispersive process, the aqueous (Th1-xCex)(OH)y·nH2O gel microspheres were washed and dried at 200 °C, calcinated and sintered. It was found that more than 99 % of the sintered microspheres maintained an excellent degree of sphericity and integrality when the parameters were properly controlled. It was found that the feeding solution preparation process was the most important and complex step to obtain uniform microspheres of good sphericity during the whole kernel fabrication process. The (Th1-xCex)O2 microspheres produced were characterized using thermogravimetric analysis, X-ray diffraction (XRD), scanning electron microscopy, and energy dispersive spectroscopy (EDS). The XRD analyses showed that all products appeared as a solid solution with a cubic fluorite structure when doped with cerium in the selective compositional range. The elemental scanning by EDS showed an excellent uniform distribution of thorium and cerium in the sintered microspheres.

Effect of internal and external gelation on the physical properties, water distribution, and lycopene encapsulation properties of alginate-based emulsion gels

It is challenging to incorporate lycopene, a strongly hydrophobic nutraceutical, into functional foods because of its low water-solubility and poor bioaccessibility. In this study, we therefore examined the potential of alginate-based emulsion gels to encapsulate and deliver lycopene. Alginate can be gelled using either internal or external gelation mechanisms, but few studies have compared the advantages and disadvantages of these two approaches for producing emulsion gels. For this reason, we compared the structure, water distribution, water mobility, and simulated digestion of lycopene-loaded emulsion gels formed by gelling alginate within the aqueous phase using either the internal or external methods. The internal gelation method produced emulsion gels that contained smaller oil droplets, and had a higher hardness, water holding capacity, and freeze-thaw stability. Moreover, the internal gelation method led to emulsion gels that had a slightly higher lycopene bioaccessibility (36.1%) than the ones formed by the external gelation method (33.4%). These findings are important for optimizing the design and fabrication of emulsion gels suitable as delivery systems for nutraceuticals in the food industry.

Synthesis, characterization, and application of external gelation of sodium alginate nanoparticles in molecular imprinting for separation and drug delivery of tenoxicam

Synthesis, characterization, and application of external gelation of sodium alginate nanoparticles in molecular imprinting for separation and drug delivery of tenoxicam

Enzymes Encapsulated within Alginate Hydrogels: Bioelectrocatalysis and Electrochemiluminescence Applications.

A simple procedure to incorporate enzymes (horseradish peroxidase, HRP, and lactate oxidase, LOx) within alginate hydrogels is reported with electrochemiluminescence (ECL) used to detect the enzymatic reactions with the corresponding substrates. First, HRP and LOx were successfully immobilized into CaCO3 microspheres, followed by the electrostatic layer-by-layer deposition of a nanoshell onto the microspheres, and finally by their dispersion into alginate solution. The as-prepared dispersion was drop cast onto the glassy carbon electrodes and cross-linked by the external and internal gelation methods using Ca2+ cations. The enzymes encapsulated within the alginate hydrogels were characterized using cyclic voltammetry and kinetic studies performed using ECL. The results showed that the enzymatic activity was significantly maintained as a result of the immobilization, with values of the apparent Michaelis-Menten constants estimated as 7.71 ± 0.62 and 8.41 ± 0.43 μM, for HRP and LOx, respectively. The proposed biosensors showed good stability and repeatability with an estimated limit of detection of 5.38 ± 0.05 and 0.50 ± 0.03 μM for hydrogen peroxide and lactic acid, respectively. The as-prepared enzymes encapsulated within the alginate hydrogels showed good stability up to 28 days from their preparation. The sensitivity and selectivity of the enzymes encapsulated within the alginate hydrogels were tested in real matrices (HRP, hydrogen peroxide, in contact lens solution; LOx, lactic acid in artificial sweat) showing the sensitivity of the ECL detection methods for the detection of hydrogen peroxide and lactic acid in real samples.

Rheology of individual chitosan and polyphenol/chitosan microparticles for food engineering

Encapsulation of perishable bioactive molecules has become a standard process in the food industry. Beads in the millimeter size range may offer technological advantage over smaller particles and nano-structured materials for encapsulation purposes because of higher volume to surface ratios, but their size might seriously affect the sensory properties of the final edible products. We investigated the rheological properties of individual beads composed of chitosan (CTS) cross-linked with sodium tripolyphosphate (TTP). We produced the beads by the external gelation method using different combinations of CTS and TTP concentrations. Analysis of raw data showed that CTS and TTP affected both the morphology and the response of the particles to mechanical load in a non proportional way. The data indicated that the mechanical properties of the beads could not be explained with the aid of standard linear viscoelastic models. We therefore exploited a recently-developed nonlinear model to analyse mechanical data collected during the stress phase and estimate viscoelastic parameters. We found a clear synergic effect of CTS and TTP concentrations on particles’ stiffness and a crossover effect on their viscosity. Two representative bioactive food phenolic compounds, i.e. chlorogenic acid and catechin, were then encapsulated into the beads. Encapsulation of chlorogenic acid and catechin dramatically altered the viscoelastic behaviour of the particles in a similar way. The particles became less stiff and viscous and more fluid-like compared to empty beads with the same CTS and TTP composition. Our results pave the way for a more accurate evaluation of sensory characteristics of novel functional foods incorporating particle carriers for bioactive molecules.

Internal/external aqueous-phase gelation treatment of soybean lipophilic protein W/O/W emulsions: Improvement in microstructure, interfacial properties, physicochemical stability, and digestion characteristics

This study aimed to examine the effects of gelation on the stability and functionality of soybean lipophilic protein (LP)-stabilized W/O/W emulsions by gelating the internal and external aqueous phases separately. Xanthan gum, gum arabic, methylcellulose, and pectin were used to gel the internal/external aqueous phase of W/O/W emulsions. The measurements of particle size, zeta potential, emulsifying properties, interfacial tension, microstructure, physicochemical stability, and digestion characteristics revealed that the internal/external aqueous-phase gelation effectively reduced the interfacial tension of emulsions, the external aqueous-phase gelation improved the interfacial protein adsorption rate of emulsion (more than 78%), and the internal aqueous-phase gelation improved the encapsulation efficiency of emulsion (more than 90%) and internal aqueous-phase retention (more than 85%). Meanwhile, both gelation treatments improved the digestion performance of emulsions, achieved the sustained release of entrapped materials, and improved their bioavailability. Briefly, the internal/external aqueous-phase gelation enhances W/O/W emulsion stability. This study enriched the means to improve the stability of W/O/W emulsions, which benefited the application and innovation of W/O/W emulsions in food processing.

Comparative of alginate/graphene oxide and alginate/magnetite graphene oxide aerogel as adsorbents

Magnetite graphene oxide (MGO) has gained attention as a potential adsorbent in wastewater treatment. In this study, incorporation of MGO into biopolymer matrix and dried by supercritical CO2 to improve the adsorption efficiency is presented. Alginate/MGO aerogel was prepared by blending the MGO with alginate and formed hydrogel by ionic crosslinking through external gelation. The blend ratio of MGO and alginate studied are comprised of 2 and 3 wt%, respectively. The hydrogel was dried by supercritical CO2 at 110 ± 5 bar and 40 °C in 4h. The physical-chemical properties of alginate/MGO adsorbent and its adsorption efficiency via removal of methylene blue (MB) are studied. The sharp curve for 30% weight loss for both types of adsorbents has been shown around 200 °C in TGA correspond to the exothermic peak form in DSC analysis. Alginate/GO and alginate/MGO are stable over temperatures of 300 and 700 °C, respectively. Alginate/GO successfully adsorbed 90% of MB concentration meanwhile the alginate/MGO had removed up to 84% of MB. Another highlighted technique is supercritical CO2 drying which considered as one of the most promising techniques to preserve the structure of aerogel with minimal shrinkage as low as 15% in comparison to ambient drying (50%).

Effects of gelation on the stability, tribological properties and time-delayed release profile of double emulsions

Due to the unique multi-chamber structure of the double emulsion (DE), gelation different compartments of double emulsions with different gelling strength offers flexible control over their encapsulation and delivery properties. Herein, the aqueous or oil phase of DE was gelled with alginate or beeswax at different gelling strength, and the effects of gelation on the processing stability, rheological and tribological properties as well as the digestion profile of double emulsions were investigated. Gelation in each phase improved the stability of DE (0,0,0), with the oil or external aqueous phase gelation being more efficient in lifting the encapsulation stability after 14 days’ storage (increased from 67.50 ± 2.47% to 86–90% and 84–90%, respectively). Under processing conditions, the oil phase gelled DE was easily destabilized when subjected to heating treatment, but maintained better stability under freeze-thaw or osmotic pressure treatment compared to the internal and external water phase gelled ones. Gelation also actively regulated the rheological and tribological properties of DE, wherein gelation in internal water phase showed the least impact on the rheological properties, gelation in the external aqueous phase and oil phase exerted more significant influence on the viscosity and the tribological properties of DE, respectively. The external water phase gelled DE manifested the time-delayed digestion profile with only 8.09 ± 0.12% of internal marker release at the end of gastric digestion and the FFA release extent was decreased by 41.66% as compared to the DE (0,0,0). The present study offers a valuable guide for rational design of double emulsions with tailor-made processing stability, oral sensation and digestive characteristics.

Structural and functional properties of alginate obtained by means of high hydrostatic pressure-assisted extraction

The effects of the high hydrostatic pressure (HPP) pre-treatment on the alginate extraction were seen to greatly depend on the recalcitrant nature of two algae species. Alginates were deeply characterized in terms of composition, structure (HPAEC-PAD, FTIR, NMR, SEC-MALS), functional and technological properties.The pre-treatment significantly increased the alginate yield in the less recalcitrant A. nodosum (AHP) also favoring the extraction of sulphated fucoidan/fucan structures and polyphenols. Although the molecular weight was significantly lower in AHP samples, neither the M/G ratio nor the M and G sequences were modified. In contrast, a lower increase in alginate extraction yield was observed for the more recalcitrant S. latissima after the HPP pre-treatment (SHP), but it significantly affected the M/G values of the resulting extract. The gelling properties of the alginate extracts were also explored by external gelation in CaCl2 solutions. The mechanical strength and nanostructure of the hydrogel beads prepared were determined using compression tests, synchrotron small angle X-ray scattering (SAXS), and cryo-scanning electron microscopy (Cryo-SEM). Interestingly, the application of HPP significantly improved the gel strength of SHP, in agreement with the lower M/G values and the stiffer rod-like conformation obtained for these samples.

Encapsulation of Bifidobacterium animalis subsp. lactis Through Emulsification Coupled with External Gelation for the Development of Synbiotic Systems

Aim of this work was the development of integrated and complex encapsulating systems that will provide more efficient protection to the probiotic strain Bifidobacterium animalis subsp. lactis (BB-12) in comparison to the conventional plain alginate beads. Within the scope of this study, the encapsulation of BB-12 through emulsification followed by external gelation was performed. For this purpose, a variety of alginate-based blends, composed of conventional and novel materials, were used. The results demonstrated that alginate beads incorporating 1% carrageenan or 2% nanocrystalline cellulose provided great protection to the viability of the probiotic bacteria during refrigerated storage (survival rates of 50.3% and 51.1%, respectively), as well as in vitro simulation of the gastrointestinal tract (survival rates of 38.7 and 42.0%, respectively). The incorporation of glycerol into the formulation of the beads improved the protective efficiency of the beads to the BB-12 cells during frozen storage, increasing significantly their viability compared to the plain alginate beads. Beads made of milk, alginate 1%, glucose 5%, and inulin 2% provided the best results in all cases. The microstructure of beads was assessed through SEM analysis and showed absence of free bacteria on the surface of the produced beads. Consequently, the encapsulation of BB-12 through emulsification in a complex encapsulating system was proved successful and effective.