Production Of Capsules Research Articles

Polymer Capsules for Enzymatic Catalysis in Confined Environments

Catalysis is at the base of a series of biological and technological application processes. In recent years, the tendency has developed to carry out catalyzed reactions within confined structures, thus forming systems called micro or nanoreactors. Compartmentalized structures are cavities delimited by a wall where specific functions are introduced with a defined concentration and in the desired sites. These containers are generally referred to as nano or microcapsules, assuming the function of reactors in the presence of chemical reactions. Among the various types of existing structures, one of the most interesting is represented by systems made with polymers. This review aims to highlight some of the current advances in the use of functionalized structures that are useful for catalysis reactions, paying particular attention to polymer capsules and enzymes. The built-up methods used for the production of polymer capsules, as well as the aspects that influence membrane permeability and reactivity to environmental conditions, are discussed. Recent advances on biocatalysis confined in polymeric capsules are illustrated, and the strengths and weaknesses of the principal nanoreactors are considered.

Monitoring the ingredient change during the production of Tan Re Qing capsules from Scutellariae Radix by HPLC-MS/MS

Tan Re Qing (TRQ), a traditional Chinese medicine formula, is composed of Scutellariae Radix and other four herbs (bear bile powder, Caprae Hircus Cornu, Lonicerae japonicae Flos and Forsythiae Fructus) used for the treatment of bronchitis and upper respiratory infection. Chemical constituents in the herb always changed in content during processing. So, in this study, the ingredient change was monitored from three froms of Scutellariae Radix, including original herb, intermediate and product (TRQ capsules) with the same batch by HPLC MS/MS. A total of 98 compounds, including 69 flavonoids, 5 phenylethanoid glucosides, 6 other compounds and 18 unknown components, were tentatively identified in Scutellariae Radix. Most minor components in Scutellariae Radix were disappeared during preparation process, and only 17 of these compounds were detected in TRQ capsules. 5,2’-Dihydroxy-7,8-dimethoxyflavone and one unknown compound were detected in the original herb and intermediate, but disappeared in the TRQ capsules. These findings indicated the productive process control is vital for risk assessment and chemical material basis, as well as the basis for quality control of TRQ capsules.

Encapsulation of oils and fragrances by core-in-shell structures from silica particles, polymers and surfactants: The brick-and-mortar concept

Colloidosomes provide a possibility to encapsulate oily substances in water in the form of core-in-shell structures. In this study, we produced microcapsules with shell from colloidal particles, where the interparticle openings are blocked by mixed layers from polymer and surfactant that prevent the leakage of cargo molecules. In other words, the particles and polymer play the role of bricks and mortar. For this goal, we used hydrophilic silica particles, which were partially hydrophobized by the adsorption of potassium oleate to enable them to stabilize Pickering emulsions. Various polymers were tested to select the most appropriate one. The procedure of encapsulation is simple and includes single homogenization by ultrasound. The produced capsules are pH responsive. They are stable in aqueous phase of pH in the range 3–6, but at pH > 6 they are destabilized and their cargo is released. With the optimized formulation of silica particles, polymer, oleate and NaCl, we were able to encapsulate various oils and fragrances, such as tetradecane, limonene, benzyl salicylate and citronellol. All of them have a limited and not too high solubility in water. In contrast, no stable microcapsules were obtained with oils that either have zero water solubility (mineral and silicone oil) or higher water solubility (phenoxyethanol and benzyl alcohol). By analysis of results from additional interfacial-tension and thin-film experiments, we concluded that a key factor for obtaining stable capsules is the irreversible adsorption of the polymer at the oil/water interface. The hydrophobization of the particles by surfactant adsorption (instead of silanization) plays an important role for the pH responsiveness of the produced capsules. The obtained information about the role of various factors for the stabilization of microcapsules, which are based on the brick-and-mortar concept, can be further used to achieve better stability; selection of polymers that are appropriate for different classes of oils, as well as for the production of smaller capsules stabilized by nanoparticles.

Wpływ warunków przechowywania na stabilność mas żelatynowych przeznaczonych do wytwarzania kapsułek miękkich

Wpływ warunków przechowywania na stabilność mas żelatynowych przeznaczonych do wytwarzania kapsułek miękkich

Computational approaches to predict the effect of shear during processing of lubricated pharmaceutical blends

In the production of pharmaceutical tablets and capsules, a lubricant such as magnesium stearate is often added to the powder blend or granulation in order to reduce friction and, in some cases, minimize sticking to the manufacturing equipment surfaces. If the lubricated blend is exposed to excessive shear during the processing steps prior to tableting or encapsulation, adverse effects on quality attributes of the final dosage form may be observed. These could include an increase in wetting contact angle, a slowdown in disintegration and/or dissolution, and a reduction in the tensile strength of compacts. In this work, two different computational modeling approaches are proposed to predict the effect of shear during the processing of lubricated pharmaceutical blends on drug product quality attributes. In this case study, an agitated powder feed system is examined, but the approach could be readily extended to other powder processing operations. First, a framework for the prediction of lubrication-based tensile strength reduction using the discrete element method (DEM) is proposed. This approach utilizes a companion study in a lab-scale, high-shear mixer to map the DEM predictions of extent of shear to an experimentally relevant tensile strength prediction. Second, a compartment model (CM) approach is proposed to model the powder flow and lubrication in the feed system. The tensile strength predictions from these two different approaches both compare favorably to experimental measurements of tensile strength.

Microencapsulation of docosahexaenoic acid (DHA) with four wall materials including pea protein-modified starch complex

Omega-3 fatty acids, specifically docosahexaenoic acid (DHA, 22 carbons and 6 double bonds) are fundamental compounds for a healthy diet. However, due to their unsaturated nature, omega fatty acid-rich oils are chemically unstable and susceptible to oxidative deterioration. The oxidation results in production of free radicals and unpleasant tastes, negatively impacting the shelf-life, sensory properties, and acceptability of food products. This study was conducted to examine the effect of wall materials on protection of DHA in canola oil against oxidation. A total of 4 wall materials including pea protein isolate (PPI), pea protein isolate - modified starch complex (PPI-MS), Tween 20, and SDS were used for microemulsion preparation with canola oil containing DHA. The freeze-dried powders were analyzed with respect to physicochemical characteristics, oxidative stability, and release properties. The results showed that the PPI-MS as a natural polymeric wall material exhibited similar or better encapsulation efficiency and acceptable level of peroxide value compared to the synthetic surfactants (Tween 20 and SDS). The utilization of protein-polysaccharide complexes enabled the incorporation of specific properties of each biopolymer to further improve emulsion stability for the production of capsules with improved oxidative stability.

On demand manufacturing of patient-specific liquid capsules via co-ordinated 3D printing and liquid dispensing

A method for the production of liquid capsules with the potential of modifying drug dose and release is presented. For the first time, the co-ordinated use of fused deposition modelling (FDM), 3D printing and liquid dispensing to fabricate individualised dosage form on demand in a fully automated fashion has been demonstrated. Polymethacrylate shells (Eudragit EPO and RL) for immediate and extended release were fabricated using FDM 3D printing and simultaneously filled using a computer-controlled liquid dispenser loaded with model drug solution (theophylline) or suspension (dipyridamole). The impact of printing modes: simultaneous shell printing and filling (single-phase) or sequential 3D printing of shell bottom, filling and shell cap (multi-phase), nozzle size, syringe volume, and shell structure has been reported. The use of shell thickness of 1.6 mm, and concentric architecture allowed successful containment of liquid core whilst maintaining the release properties of the 3D printed liquid capsule. The linear relationship between the theoretical and the actual volumes from the dispenser reflected its potential for accurate dosing (R2 = 0.9985). Modifying the shell thickness of Eudragit RL capsule allowed a controlled extended drug release without the need for formulation change. Owing to its low cost and versatility, this approach can be adapted to wide spectrum of liquid formulations such as small and large molecule solutions and obviate the need for compatibility with the high temperature of FDM 3D printing process. In a clinical setting, health care staff will be able to instantly manufacture in small volumes liquid capsules with individualised dose contents and release pattern in response to specific patient's needs.

Environmental influences on growth and reproductive maturation of a keystone forest tree: Implications for obligate seeder susceptibility to frequent fire

Abstract Anthropogenic modifications to climate and natural fire regimes are occurring globally, leading to the production of environments that may be unsuitable for some species. Fire-intolerant plant species that rely on specific fire regimes for reproduction are at risk of population decline when successive fires occur in less than the time taken to produce seed. Quantifying key fire-related life history traits in such species is therefore critical for developing models of population viability, species distributions and ecosystem persistence. We studied the Australian mountain ash (Eucalyptus regnans), the world’s tallest angiosperm and an ecologically and economically important keystone species. We tested whether mountain ash populations exhibit variation in susceptibility to increasing fire frequency by characterising the response of key vital rates to stand age (time since fire) under different environmental conditions. We found that the time taken to produce seed varied geographically. Mean growth rates were greater in areas receiving higher levels of solar radiation, a trend that became stronger with tree age. Tree size and age had the strongest influence on the production of fruit capsules. Mature fruit capsules were found in trees as young as 11 years old, but stands may not contain reproductively viable seed crops until they are more than 21 years old. Our results show that environmental factors influence the primary juvenile period of a keystone obligate seeder, in turn affecting the time taken for a population to develop a reproductively viable seed amount of seed. Reduced fire return intervals may therefore constrain the species’ realised niche (and geographic distribution) to areas where it can tolerate shorter fire return intervals due to faster growth and maturation. We suggest that populations of obligate seeders that reach reproductive viability faster are thus more likely to persist when exposed to multiple fires in short succession. Intra-stand variation in seed crops suggests that selection could also act on rapidly-maturing individuals, resulting in some populations exhibiting high levels of precocious reproductive activity.

Production, deformation and mechanical investigation of magnetic alginate capsules

In this article we investigated the deformation of alginate capsules in magnetic fields. The sensitivity to magnetic forces was realised by encapsulating an oil in water emulsion, where the oil droplets contained dispersed magnetic nanoparticles. We solved calcium ions in the aqueous emulsion phase, which act as crosslinking compounds for forming thin layers of alginate membranes. This encapsulating technique allows the production of flexible capsules with an emulsion as the capsule core. It is important to mention that the magnetic nanoparticles were stable and dispersed throughout the complete process, which is an important difference to most magnetic alginate-based materials. In a series of experiments, we used spinning drop techniques, capsule squeezing experiments and interfacial shear rheology in order to determine the surface Young moduli, the surface Poisson ratios and the surface shear moduli of the magnetically sensitive alginate capsules. In additional experiments, we analysed the capsule deformation in magnetic fields.In spinning drop and capsule squeezing experiments, water droplets were pressed out of the capsules at elevated values of the mechanical load. This phenomenon might be used for the mechanically triggered release of water-soluble ingredients. After drying the emulsion-filled capsules, we produced capsules, which only contained a homogeneous oil phase with stable suspended magnetic nanoparticles (organic ferrofluid). In the dried state, the thin alginate membranes of these particles were rather rigid. These dehydrated capsules could be stored at ambient conditions for several months without changing their properties. After exposure to water, the alginate membranes rehydrated and became flexible and deformable again. During this swelling process, water diffused back in the capsule. This long-term stability and rehydration offers a great spectrum of different applications as sensors, soft actuators, artificial muscles or drug delivery systems.

Development of a multilayer structure for power unit acoustic shielding

The article presents the theoretical aspects of noise protection device development for the power unit of trucks, as well as the practical research and experimental development of materials for the production of acoustic capsules. The studies of physical-mechanical, heat-conducting, sound-absorbing, vibration-absorbing properties of various polyurethane materials were carried out. The prospect of polymeric composite materials use as the acoustic protection of trucks has been revealed. One of the main problems of modern ecology is the noise pollution of the environment. More and more people feel the negative impact of noise on general health condition. Transport noise, as the main source, prevails in industrial environment [1]. The mechanisms and the systems of vehicle power units are the main source of both external and internal noise of transport. The requirements for the noise of cars throughout the history of vehicles are tightened constantly. Nowadays, the noise of vehicles is normalized by the national standard of Russian Federation GOST R 41.51 (UNECE Regulation No. 51). According to the document, the maximum value of the total noise level is in the range of 74-80 dBA

Microwave Extraction of Gallic Acid Equivalent of Total Flavonoids from Nigella sativa

Unfortunately, cancer is the most widespread disease in worldwide. Colorectal cancer is declared as the third most common cancer type. The usage of controlled-drug-releasing capsules for treating the cancer diseases has becoming more and more popular in the whole world. In the production of drug raw material, the first operation is an extraction of the phytochemicals from the herbal plant. The yield of the extraction operation is an important step for the economical and efficient production of such capsules. Thus the aim of this study was to optimize the microwave extraction of total flavonoids from Nigella sativa with methanol by using Response Surface Methodology based on Box-Behnken design. Microwave extraction experiments had been carried out with the parameters of microwave power, solid/liquid ratio and the and the application time. The optimum values were determined as 0.62 kW, 1/(47) g/mL, and 10.84 second, respectively. According to the quadratic surface of the extraction yield depending on those parameters, 309.60 mg/100g of gallic acid equivalent of total flavonoids can be obtained at the optimum conditions. As a result of the statistical analysis, this function was found as capable of expressing the effect of the parameters on the amount of total flavonoid production in industry. Nowadays, drying of the extracts and loading of the aqueous solutions of them into the prebiotic-coated probiotic capsules have been under consideration.

Synthesis and characterisation of robust emulsion-templated silica microcapsules

Robust silica microcapsules were synthesised using an emulsion template via a seeded growth strategy. Multiple additions of the silica precursor tetraethyl orthosilicate (TEOS) were observed to result in a number of physical and property changes of the capsule shells as compared to a single coating. Scanning electron microscopy indicated a morphological transition from a smooth to a roughened surface. Improved cargo retention and consolidation of the pore structure of the silica shells were observed using dye release experiments and nitrogen porosimetry respectively. In comparison to a typical hollow silica shell synthesis procedure, this one-pot loading and synthesis allows the simple production of robust capsules that are capable of sustained release, using mild conditions and reagents.

Optimizing surfactant ratio for the production of capsules containing glicazide using solid dispersion technique

The objective of this study was to formulate and prepare gliclazide capsule by solid dispersion method using different surfactants and their in vitro evaluation. Solubilising capacity of polyethylene glycol (PEG 6000, PEG 20000) and polyvinylpyrrolidone (PVP K 30) was determined at 2% concentration where gliclazide was used as a model drug and water was used as control for comparison. Results showed that PVP K 30 exhibited maximum solubilising capacity. Fusion method of solid dispersion was adopted for preparation of capsules using PEG 6000 & PEG 20000 in different ratios. Although these agents are claimed to be good surfactants but our results showed that, the highest cumulative drug release was 1.81 % for gliclazide and PEG 6000 in a ratio of 1:6. The flow property of capsule granules was determined by angle of repose. The capsules were also subjected to weight uniformity test, disintegration test and moisture permeation test and the chemical analysis of solid dispersions were done by FTIR. From this study, it can be concluded that it is possible to formulate and prepare gliclazide capsule by using solid dispersion method.

Oil encapsulation in core–shell alginate capsules by inverse gelation. I: dripping methodology

The production of capsules by inverse gelation consists of adding dropwise oil containing calcium dispersion into an alginate bath. A dripping technique to produce capsules from oil-in-water (O/W) emulsions was proposed by Abang. However, little is known about the oil encapsulation using water-in-oil (W/O) emulsions. This work aims to develop a new method of W/O emulsions encapsulation by inverse gelation. The success of the W/O emulsion encapsulation is due to three factors: 1) use of an emulsion with moderate stability (50 min); 2) production of an emulsion with at least 90 g/L of CaCl2 and 3) addition of ethanol (20% v/v) into the alginate bath. Both wet and dry capsules were obtained with a spherical shape with diameters of 7 and 3.6 mm, respectively. All volume of oil was encapsulated and the oil loading in the wet and dry capsules was of 23 and 68% v/v, respectively.

Controlled production of sub-millimeter liquid core hydrogel capsules for parallelized 3D cell culture.

Liquid core capsules having a hydrogel membrane are becoming a versatile tool for three-dimensional culture of micro-organisms and mammalian cells. Making sub-millimeter capsules at a high rate, via the breakup of a compound jet in air, opens the way to high-throughput screening applications. However, control of the capsule size monodispersity, especially required for quantitative bioassays, was still lacking. Here, we report how the understanding of the underlying hydrodynamic instabilities that occur during the process can lead to calibrated core-shell bioreactors. The requirements are: i) damping the shear layer instability that develops inside the injector arising from the co-annular flow configuration of liquid phases having contrasting viscoelastic properties; ii) controlling the capillary instability of the compound jet by superposing a harmonic perturbation onto the shell flow; iii) avoiding coalescence of drops during jet fragmentation as well as during drop flight towards the gelling bath; iv) ensuring proper engulfment of the compound drops into the gelling bath for building a closed hydrogel shell. We end up with the creation of numerous identical compartments in which cells are able to form multicellular aggregates, namely spheroids. In addition, we implement an intermediate composite hydrogel layer, composed of alginate and collagen, allowing cell adhesion and thus the formation of epithelia or monolayers of cells.

On-chip encapsulation via chaotic mixing

A microfluidic device for production of uniform size capsules with a prescribed membrane thickness is described. It is versatile, novel and suitable for various polymerization reactions. Parameters such as polymerization time and reagent concentrations can be precisely tuned to control the membrane properties. The device features a part which allows to overcome the diffusion barrier by initiating interfacial polymerization via chaotic mixing. It also allows the termination of the reaction and the collection of the resulting capsules. We observe different typical dynamical phenomena occurring in capsules during their flow along the microchannel, namely wrinkling of the membrane, parachute and bullet shapes and bursting of the capsules due to strong hydrodynamical flow. In addition to production, the monitoring of capsule dynamics in flow gave a possibility to estimate the elastic surface modulus \(E_{{\rm S}}\) and the membrane thickness t. We found that \(E_{{\rm S}}\) can be as low as 6 × 10−3 N m−1 and that the thickness can be below 100 nm. This microfluidic device is therefore capable of producing uniform size capsule solutions with suitable membrane properties for the controlled release of drugs, and as a model system of red blood cells for microhydrodynamics experiments.

Pill testing at music festivals: can we do more harm?

Pill testing at music festivals: can we do more harm?

Nonaxisymmetric disturbances in compound liquid jets falling under gravity.

The disintegration of a compound thread of fluid can be utilized in a wide variety of applications including the production of compound droplets or capsules. In this paper we investigate the linear instability of a compound inviscid liquid jet falling under gravity in a surrounding gas with respect to nonaxisymmetric waves. We derive an analytical expression for the dispersion relation, which takes into account the non-uniform nature of the jet, and which we then solve numerically. Particular attention is paid to investigating the effects of the liquid-to-gas density ratio on the growth and development of different wave modes as well as the influence of gravity. Our results show that there exists some nonaxisymmetric long wavelength disturbances that are more unstable than their asymmetric equivalents and that the influence of gravity can alter the behavior of these modes.

Monodisperse core-shell alginate (micro)-capsules with oil core generated from droplets millifluidic

Droplets millifluidic devices are efficient tools to produce monodisperse emulsions that can be used as template for the production of core-shell capsules. This work aims to develop an original alginate inverse gelation method to produce (micro)-capsules with a narrow size distribution using droplets millifluidic. Water-in-oil (W/O) emulsion dispersed phase containing Ca2+ ions was directly injected into a continuous alginate phase to generate a secondary W/O/W emulsion. Due to the cross-linking of alginate molecules by Ca2+ ions release, core-shell (micro)-capsules were formed with a very high oil loading. This study demonstrated for the first time the production of (micro)-capsules based on the inverse gelation mechanism using a simple millifluidic device. Monodisperse core-shell capsules with sizes ranging from 140 μm to 1.4 mm were produced by tuning flow rates of the continuous and dispersed phases and by varying internal diameter of the capillary tubing. The use of millifluidic devices paves the way to an integrative formulation of core-shell materials with very large characteristic sizes and new complex architectures. This should lead to the rapid emergence of new products in cosmetics or food where the texture and visual aspect play a key role for sale.

Germline Defects Caused by Smed-boule RNA-Interference Reveal That Egg Capsule Deposition Occurs Independently of Fertilization, Ovulation, Mating, or the Presence of Gametes in Planarian Flatworms.

Few animals are known to lay eggs in the absence of ovulation or copulation, as it is presumably energetically wasteful and subjected to negative selection. Characterization of Smed-boule, a member of the DAZ family of germline RNA-binding proteins, revealed that egg capsule (or capsule) production and deposition occurs independently of the presence of gametes in the planarian flatworm Schmidtea mediterranea. Reduction of Smed-boule expression by RNA-interference (RNAi) causes ablation of spermatogonial stem cells and the inability of ovarian germline stem cells to undergo oogenesis. Although animals subjected to Smed-boule RNAi lose their gametes and become sterile, they continue to lay egg capsules. Production of sterile capsules is even observed in virgin Smed-boule(RNAi) and control planarians maintained in complete isolation, demonstrating that egg production in S. mediterranea occurs independently of ovulation, fertilization, or mating. Evidence suggests that this is a conserved feature amongst Platyhelminthes, and therefore relevant to the pathology and dissemination of parasitic flatworms. These findings demonstrate that Smed-boule functions at different stages during male and female germline stem cell development, and also demonstrate that egg capsule production by planarian flatworms occurs independently of signals produced by mating or ova.