External Gelation Research Articles

Development of a scalable procedure for fine calcium alginate particle preparation

A simple and scalable two step method for the preparation of loaded calcium alginate fine powder was developed. Spray-dryer was used to prepare sodium alginate particles and all the spraying parameters were studied to optimize the powder characteristics. The particles were gelified successively by external gelation in a calcium chloride solution. Two model active pharmaceutical ingredients were encapsulated in alginate particles (i.e., bacitracin and bovine serum albumin). The obtained powders show the suitable characteristics for pulmonary drug delivery.

The in vivo performance of magnetic particle-loaded injectable, in situ gelling, carriers for the delivery of local hyperthermia

We investigated the use of in situ implant formation that incorporates superparamagnetic iron oxide nanoparticles (SPIONs) as a form of minimally invasive treatment of cancer lesions by magnetically induced local hyperthermia. We developed injectable formulations that form gels entrapping magnetic particles into a tumor. We used SPIONs embedded in silica microparticles to favor syringeability and incorporated the highest proportion possible to allow large heating capacities. Hydrogel, single-solvent organogel and cosolvent (low-toxicity hydrophilic solvent) organogel formulations were injected into human cancer tumors xenografted in mice. The thermoreversible hydrogels (poloxamer, chitosan), which accommodated 20% w/v of the magnetic microparticles, proved to be inadequate. Alginate hydrogels, however, incorporated 10% w/v of the magnetic microparticles, and the external gelation led to strong implants localizing to the tumor periphery, whereas internal gelation failed in situ. The organogel formulations, which consisted of precipitating polymers dissolved in single organic solvents, displayed various microstructures. A 8% poly(ethylene-vinyl alcohol) in DMSO containing 40% w/v of magnetic microparticles formed the most suitable implants in terms of tumor casting and heat delivery. Importantly, it is of great clinical interest to develop cosolvent formulations with up to 20% w/v of magnetic microparticles that show reduced toxicity and centered tumor implantation.

Monodisperse Cell-Encapsulating Peptide Microgel Beads for 3D Cell Culture

This paper describes a method to produce monodisperse cell-encapsulating microgel beads composed of a self-assembling peptide gel for three-dimensional (3D) cell culture. We used a 3D microfluidic axisymmetric flow-focusing device with an external gelation method. The finely powdered salts were dispersed into a continuous phase, and the salts induced the gelation when in contact with the peptide solution. Over 93% of the cells survived after the encapsulation, and the cells migrated and grew within the gels. Applications of our cell-encapsulating beads include bead-based cell assays in drug testing and engineering tissue constructs.

Preparation of uniformly sized alginate microspheres using the novel combined methods of microchannel emulsification and external gelation

The purpose of this study was to prepare alginate (ALG) microspheres with narrow size distribution using a combination of microchannel (MC) emulsification technique and external gelation method. ALG solution was dispersed as water-in-oil (W/O) emulsion droplets in iso-octane containing 5 wt% Span 85 as the immiscible continuous phase via MC emulsification technique using hydrophobic MC array. The MC array used in this experiment is a grooved-type MC consisting of 1070 channels fabricated on a 25 mm × 28 mm silicon microchip. The monodisperse W/O emulsion droplets generated from the MCs were in the mean particle diameter ( d av) range of 18–22 μm and coefficient of variation (CV) of 5–26% at the ALG concentrations of 0.5–3.0 wt% and flow rates of 0.05–0.4 mL/h. The d av of the emulsion droplets hardly changed below a dispersed phase threshold flow rate of 0.2 mL/h but gradually became smaller when the dispersed phase concentration was increased. The resulting emulsion droplets were then congealed to form rigid ALG gel particles by reacting them with calcium chloride (CaCl 2) solution. Gelation of the ALG droplets by calcium ion (Ca 2+) resulted in shrinkage of its d av, forming uniformly sized ALG microspheres with an average diameter of 6.2 μm and a CV of below 10% at the ALG concentration of 3 wt%.

Characteristics and antioxidant activity of catechin-loaded calcium pectinate gel beads prepared by internal gelation

Catechin-loaded calcium pectinate gel beads prepared by internal gelation were characterized for their catechin entrapment efficiency and release behavior. The entrapment efficiency was higher when the beads were prepared with a lower catechin-to-pectin ratio, shorter gelling time, higher pectin concentration, and lower acetic acid concentration. The entrapment efficiency was much higher under all tested conditions, when the beads were prepared by internal gelation instead of external gelation. The catechin release was slower for the beads prepared with lower catechin-to-pectin ratio, longer gelling time, and higher concentrations of pectin and acetic acid in both simulated gastric and intestinal fluids. Antioxidant power of catechin was effectively maintained in alkaline simulated intestinal fluid when catechin was entrapped within the beads, compared to cases where it was not entrapped, indicating that the beads can protect catechin molecules from the alkaline environment and release them in a sustained fashion.

Preparation and Characterization of Coacervate Microcapsules for the Delivery of Antimicrobial Oyster Peptides

Oyster peptides-loaded alginate/chitosan/starch microcapsules were prepared using external gelation method and internal emulsion gelation method. The solution of oyster peptides complexes was encapsulated into the microcapsules, which endowed the microcapsules with intestine passive targeting properties. The swelling behavior, encapsulation efficiency, and release behavior of oyster peptides from the microcapsules at different pH values were investigated. The microcapsules exhibited sustained release of the peptides in intestinal medium, and the release rate could be regulated by the pH value: in simulated gastric fluid, the release rate was greatly decreased, and in simulated body fluid and intestinal fluid, the microcapsules exhibited a sustained release in 24 h with different release rates. The microspheres were characterized by Fourier transform infrared. The results suggested that the alginate/chitosan/starch microcapsules could be a suitable copolymeric carrier system for intestinal protein or peptides delivery in the intestine.

Rapid exchange of oil-phase in microencapsulation chip to enhance cell viability

This paper describes a microfluidic device for the microencapsulation of cells in alginate beads to enhance cell viability. The alginate droplet including cells was gelified with calcified oleic acid, using two-phase microfluidics. The on-chip gelation had generated monodisperse spherical alginate beads, which could not be readily obtained via conventional external gelation in a calcium chloride bath. However, the prolonged exposure of encapsulated cells to the toxic oil phase caused serious damage to the cells. Therefore, we proposed the formulation of a rapid oil-exchange chip which transforms the toxic oleic acid to harmless mineral oil. The flushing out of oleic acid after the gelation of alginate beads effected a dramatic increase in the viability of P19 embryonic carcinoma cells, up to 90%. The experimental results demonstrated that the cell viability was proportional to the flow rate of squeezing mineral oil.

Alginate–poloxamer microparticles for controlled drug delivery to mucosal tissue

Purpose: The aim of this study was to prepare and characterize novel hydrogel-based delivery systems allowing for the controlled release of drugs to mucosal surfaces. Methods: Terbutaline sulfate and bovine serum albumin (BSA)-loaded alginate–poloxamer microparticles were prepared by a w/o-emulsion- and external gelation method. The microparticles were characterized by optical and scanning electron microscopy, laser light diffraction, atomic absorption spectroscopy, energy-dispersive X-ray analysis, via complexation with 1,9-dimethyl methylene blue and using dialysis bags as well as modified Franz diffusion cells for in vitro drug-release measurements. Results: Using heptane as organic phase, homogeneous and almost spherical microparticles were obtained with a high-loading efficiency (>90%). The resulting drug-release patterns could effectively be adjusted by varying the “alginate:poloxamer” blend ratio. In addition, the particle size, morphology, calcium and chloride content as well as alginate-release rates could be altered. Erosion was the predominant release mechanism for BSA. Special attention needs to be paid to the microparticle recovery procedure, which can significantly affect key properties such as the resulting drug-release patterns. Conclusions: The novel hydrogel-based microparticles offering mild conditions for incorporated drugs (e.g., proteins) provide an interesting potential as controlled delivery systems for mucosal surfaces.

Mesoporous Zirconium Titanium Oxides. Part 2: Synthesis, Porosity, and Adsorption Properties of Beads

Mesoporous zirconium titanium mixed-oxide beads having disordered wormhole textures and mole fractions of Zr (x) ranging from x=0.25 to 0.67 have been prepared. The bead preparation method combined the forced hydrolysis of mixtures of zirconium-titanium alkoxides in the presence of long-chain carboxylates with external gelation. Uniformly sized beads could be produced in the size range 0.5-1.1 mm by varying the droplet size and viscosity of the mixed-oxide sol, thus making them suitable for large-scale column chromatographic applications. The beads exhibited narrow pore size distributions with similar mean pore diameters of around 3.7 nm. The specific surface areas of the beads were linked to the Zr mole fraction in the precursor solution and were generally greater than 350 m2/g for x=0.5. A combination of scanning transmission electron microscopy and X-ray absorption fine structure analysis indicated that the pore walls of the beads were composed of atomically dispersed Zr and Ti to form a continuous network of Zr-O-Ti bonds. Mass transport in the beads was evaluated by monitoring the kinetics of vanadate and vanadyl adsorption at pH 10.5 and 0.87, respectively.

Effect of the gelation process on the production of alginate microbeads by microfluidic chip technology

The present paper reports the production of Ba-alginate microspheres by microfluidic chip technology. The general production strategy is based on the formation of an alginate multiphase flow by a 'Y' junction squeezing mechanism. Special emphasis is given to the relationship existing between the gelation process and the final morphological characteristics of the produced microbeads. A series of different gelation strategies, namely: 'external gelation', 'internal gelation' and 'partial gelation' were compared in terms of size, size distribution and morphology of the produced microbeads.

Multi-Unit Floating Alginate System: Effect of Additives on Ciprofloxacin Release

In an attempt to fabricate floating beads of ciprofloxacin, drugloaded alginate beads were prepared by simultaneous external and internal gelation. The effect of blending of alginate with gellan, hydroxypropyl methylcellulose, starch, and chitosan on the bead properties were evaluated. Beads were spherical with incorporation efficiency in the range of 52.81 ± 2.64 to 78.95 ± 1.92%. Beads exhibited buoyancy over a period of 7–24 hr based on the formulation variables. In vitro release of ciprofloxacin from the alginate beads in simulated gastric fluid (SGF) (0.1 N HCl, pH 1.2), was influenced significantly (p < 0.001) by the properties and concentration of additives. Among the polymers incorporated into alginate beads. Hydroxy propyl methylcellulose (HPMC) provided an extended release over 7 hr. The drug release predominately followed Higuchi's square root model.

Diffusion of Acetic Acid Across Oil/Water Interface in Emulsification-Internal Gelation Process for Preparation of Alginate Gel Beads

Abstract Alginate has been widely used in cell microencapsulation and drug delivery systems in the form of gel beads or microcapsules. Although an alternative novel emulsification-internal gelation technology has been established and both the properties and the potential applications of the beads in drug delivery systems have been studied, the mechanism has not been well understood compared with the traditional droplet method (external gelation technology). On the basis of our previous knowledge that the novel technology is composed of complicatedly consecutive processes with multistep diffusion and reaction, and the diffusion of acetic acid across oil/water interface being the prerequisite that determines the occurrence and rate for the reactions and the structures and properties of final produced gel beads, a special emphasis was placed on the diffusion process. With the aid of diffusion modeling and simple experimental design, the diffusion rate constant and diffusion coefficient of acetic acid across oil/water interface were determined to be in the orders of magnitude of 10 −6 and 10 −16 , respectively. This knowledge will be of particular importance in understanding and interpreting the formation, structure of the gel beads and the relationship between the structure and properties and guiding the preparation and quality control of the gel beads.

A study of function mechanism of hemxamethyl tetra-amine in gelation process of uranium

The UO 2 ceramic microspheres are the most important materials in the spherical fuel elements for high temperature reactor (HTR). A process for preparation of UO 2 kernels known as total gelation process of uranium (TGU) was developed as the production process of 10 mW HTR at Tsinghua University. The TGU process is based on the traditional sol-gel process, external gelation process and internal gelation process of uranium (EGU and IGU), which implies that the gelation action is initiated both by ammonia out of the gel particles and hemxamethyl tetra-amine (HMTA) inside the gel particles. The gelation behavior and the properties of uranium microspheres were investigated of the solution with and without HMTA. It is observed that good spherical particles can be obtained without HMTA in the sol, which indicates a more controllable and industrialized route will be set up. Contrasts between this route and the traditional EGU were also listed.

Mechanisms of external and internal gelation and their impact on the functions of alginate as a coat and delivery system

The mechanisms of internal and external gelation and their impact on alginate in its use as a coat and as a delivery system for drugs and living cells were investigated. Surface topography, thickness, mechanical and permeation properties, drug encapsulation efficiency and drug release profiles of alginate matrices were evaluated. Comparable extent of cross-linkages was produced by the two gelation methods as indicated by comparable Ca 2+ contents between externally and internally cross-linked films but the distributions of cross-linkages were different. External cross-linking produced thinner films with smoother surface, greater matrix strength, stiffness and permeability than internally cross-linked films. Externally cross-linked micropellets were also capable of greater drug encapsulation efficiency and slower drug release rate. The differences in the properties observed were due to the different gelation mechanisms involved and the physical form of the matrix produced. External gelation is the preferred method in producing cross-linked alginate for coating and encapsulation purposes.

External Gelation 방법을 이용한 구형 UO3Gel 입자 제조

HTGR (High Temperature Gas-cooled Reactor) is spotlighted to next generation nuclear power plant for producing the clean hydrogen gas and the electricity. In this study, the spherical UO₃ gel particles were prepared by the external gelation process, and the characteristics of these particles were analyzed the particle shape, composition of precipitate, and thermal decomposition characteristics with the Streoscope, FT-IR, and X-ray diffractometer. Raw material of the ADUN (Acid Deficient Uranyl Nitrate) solution, which has [NO₃]/[U] mole ratio = 1.75, was obtained from dissolution of the U₃O 8 powder with concentrated HNO₃, and its concentration is 3.5 M-U/l. The broth solution is prepared with the ADUN, urea, PVA, and THFA solution. The droplets of the broth solution was made through a nozzle system. From this study, we obtained the following results; 1) an externel chemical gelation process is a suitable method in the spherical UO₃ particle production, 2) the particle shape are changed by an urea mixing time, THFA volume, and the viscosity of the broth solution, 3) the amorphous UO₃ particles obtained from these experiments was converted to U₃O 8 and then UO₂ by heat treatment in hydrogen atmosphere at 600℃.

Fabrication Routes for Yttria‐Stabilized Zirconia Suitable for the Production of Minor Actinide Transmutation Targets

The actual fabrication processes of targets for the transmutation of actinides in nuclear reactors will need to be dust‐free and compatible with automation and remote operation. The developments reported here mark an important technical breakthrough in the fabrication of highly active materials. The sol–gel external gelation, modified by the addition of carbon, and infiltration methods have been used here to produce high‐quality, dust‐free yttria‐stabilized zirconia beads, with excellent compaction and sintering properties. Furthermore, the beads produced in this way have higher porosity, which permits the infiltration of hitherto unattainable quantities of the actinide.

Preparation of TiO 2–SiO 2 mixed gel spheres for strontium adsorption

A simple external gelation process, taking full advantage of the gelation features of titanium and silica, was developed to prepare TiO 2–SiO 2 mixed gel spheres suitable for strontium adsorption. The source solutions used for the process were prepared from different mixtures of 1 M TiCl 4 and 1 M Na 2SiO 3 solutions and converted into droplets in a gelation column. The suitable spheres for strontium adsorption were obtained using a hexone (methyl isobutyl ketone) solution as the drop formation medium and ammonia as the gelling agent. The mixed oxide gels were identified and characterized by DTA/TGA, FTIR and XRD analysis. The parameters affecting the strontium adsorption, such as weight ratio of TiO 2, pH, temperature, shaking time and selectivity towards competing ions were investigated. Sorption data have been interpreted in terms of Freundlich, Langmuir and Dubinin–Radushkevich equations. Thermodynamic parameters for the sorption system have been determined at four different temperatures. The value of Δ H° = 39.553 kJ/mol and Δ G° = −16.687 kJ/mol at 296 K prove that the sorption of strontium on mixed oxide gel is an endothermic and a spontaneous process.

Preparation of UO2 Kernel for HTR-10 Fuel Element

A 10 MW high temperature gas-cooled reactor (HTR-10) was constructed in Institute of Nuclear Energy Technology (INET) of Tsinghua University, China. HTR-10 reached its first criticality successfully in December, 2000 and realized its full power operation in the beginning of 2003. Fabrication technology for HTR-10 spherical fuel element has been established and developed in INET through a lot of R&D activities during the past 20 years. A process known as total gelation process of uranium (TGU) has been developed to prepare UO2 kernel for HTR-10 fuel element in INET. The TGU process combined advantages of both external gelation and internal gelation method of conventional sol-gel process. The sol prescription consists of not only urea, polyvinylalcohol (PVA), tetrahydrofurfuyl alcohol (THFA), but also hexamethylene tetra-amine (HMTA) that is always employed in internal gelation process. The TGU process and facilities are described in this paper. Fuel kernel production for HTR-10 fuel element using this TGU process has completed up to April, 2002. This paper also reported the quality inspection data of kernel production.

Obtenção de microesferas de (U,Th)O2 para o combustível do reator nuclear de alta temperatura

Variantes do Processo Sol-Gel foram utilizadas com sucesso para obter microesferas de (Th,U)O2 com os requisitos exigidos para seu uso em reatores HTGR. O Processo Hidrólise foi empregado para obtenção de microesferas de UO2 e o Processo de Gelação Externa foi empregado para obtenção de microesferas de (Th,U)O2 com teores de urânio de até 25%. O Processo Hidrólise ainda necessita de otimização das condições de síntese.

Swelling behaviour of alginate–chitosan microcapsules prepared by external gelation or internal gelation technology

Swelling behaviour is one of the important properties for microcapsules made by hydrogels, which always affects the diffusion and release of drugs when the microcapsules are applied in drug delivery systems. In this paper, alginate–chitosan microcapsules were prepared by different technologies called external or internal gelation process respectively. With the volume swelling degree ( S w) as an index, the effect of properties of chitosan on the swelling behaviour of both microcapsules was investigated. It was demonstrated that the microcapsules with low molecular weight and high concentration of chitosan gave rise to low S w. Considering the need of maintaining drug activity and drug loading, neutral pH and short gelation time were favorable. It was also noticed that S w of internal gelation microcapsules was lower than that of external gelation microcapsules, which was interpreted by the structure analysis of internal or external gelation Ca–alginate beads with the aid of confocal laser scanning microscope.