Rheological evaluation of inter-grade and inter-batch variability of sodium alginate

Polymeric excipients are often the least well-characterized components of pharmaceutical formulations. The aim of this study was to facilitate the QbD approach to pharmaceutical manufacturing by evaluating the inter-grade and inter-batch variability of pharmaceutical-grade polymeric excipients. Sodium alginate, a widely used polymeric excipient, was selected for evaluation using appropriate rheological methods and test conditions. The materials used were six different grades of sodium alginate and an additional ten batches of one of the grades. To compare the six grades, steady shear measurements were conducted on solutions at 1%, 2%, and 3% w/w, consistent with their use as thickening agents. Small-amplitude oscillation (SAO) measurements were conducted on sodium alginate solutions at higher concentrations (4–12% w/w) corresponding to their use in controlled-release matrices. In order to compare the ten batches of one grade, steady shear and SAO measurements were performed on their solutions at 2% w/w and 8% w/w, respectively. Results show that the potential interchangeability of these different grades used as thickening agents could be established by comparing the apparent viscosities of their solutions as a function of both alginate concentration and shear conditions. For sodium alginate used in controlled-release formulations, both steady shear behavior of solutions at low concentrations and viscoelastic properties at higher concentrations should be considered. Furthermore, among batches of the same grade, significant differences in rheological properties were observed, especially at higher solution concentrations. In conclusion, inter-grade and inter-batch variability of sodium alginate can be determined using steady shear and small-amplitude oscillation methods.     

Water-soluble polymers in agriculture: xanthan gum as eco-friendly alternative to synthetics

Water-soluble polymers (WSPs) are a versatile group of chemicals used across industries for different purposes such as thickening, stabilizing, adhesion and gelation. Synthetic polymers have tailored characteristics and are chemically homogeneous, whereas plant-derived biopolymers vary more widely in their specifications and are chemically heterogeneous. Between both sources, microbial polysaccharides are an advantageous compromise. They combine naturalness with defined material properties, precisely controlled by optimizing strain selection, fermentation operational parameters and downstream processes. The relevance of such bio-based and biodegradable materials is rising due to increasing environmental awareness of consumers and a tightening regulatory framework, causing both solid and water-soluble synthetic polymers, also termed ‘microplastics’, to have come under scrutiny. Xanthan gum is the most important microbial polysaccharide in terms of production volume and diversity of applications, and available as different grades with specific properties. In this review, we will focus on the applicability of xanthan gum in agriculture (drift control, encapsulation and soil improvement), considering its potential to replace traditionally used synthetic WSPs. As a spray adjuvant, xanthan gum prevents the formation of driftable fine droplets and shows particular resistance to mechanical shear. Xanthan gum as a component in encapsulated formulations modifies release properties or provides additional protection to encapsulated agents. In geotechnical engineering, soil amended with xanthan gum has proven to increase water retention, reduce water evaporation, percolation and soil erosion – topics of high relevance in the agriculture of the 21st century. Finally, hands-on formulation tips are provided to facilitate exploiting the full potential of xanthan gum in diverse agricultural applications and thus providing sustainable solutions.     

改性黄原胶酯化条件的优化及结构的表征

为了提高黄原胶的速溶性和粘度,将黄原胶进行改性处理。将黄原胶与马来酸酐进行酯化反应,探讨了黄原胶与马来酸酐摩尔比、反应时间和反应温度等因素的影响,以取代度为指标,利用响应面方法确定,该酯化反应的最优条件为:黄原胶与马来酸酐摩尔比1∶11.5、反应时间24.4 h、反应温度66℃。对改性黄原胶进行红外光谱、光散射和X-射线衍射等结构表征,表明酯化改性成功,且进一步解释了速溶性和粘度提高的原因。改性黄原胶细胞毒性实验,显示无毒性。结果表明,改性黄原胶的速溶性和粘度有很大提高,0.2%改性黄原胶的速溶性和粘度较对照提高了近3倍,在食品、药品等领域具有潜在的应用价值。     

Genetic engineering of polysaccharide structure: production of variants of xanthan gum in Xanthomonas campestris.

Xanthan gum is an extracellular heteropolysaccharide produced by the bacterium Xanthomonas campestris. Xanthan has wide commercial application as a viscosifier of aqueous solutions. Previously, through genetic engineering, a set of mutants defective in the xanthan biosynthetic pathway has been obtained. Certain mutants were shown to synthesize and polymerize structural variants of the xanthan repeating unit and thus produce "variant xanthans". Initial studies of solution viscosities of these polymers, presented here, indicate that the variants have rheological properties similar to, but not identical with, xanthan. These results indicate that acetylation and pyruvylation can affect the viscometric properties of xanthan. Specifically, the presence of pyruvate increases viscosity, whereas acetate decreases viscosity. In addition, the elimination of sugar residues from xanthan side chains also has a major effect on viscosity. Compared to wild-type xanthan, polymer lacking the terminal mannose (polytetramer) is a poor viscosifier. In contrast, polymer lacking both the terminal mannose and glucuronic acid (polytrimer) is a superior viscosifier, on a weight basis. There is a negative effect of acetylation on the viscosity of polytetramer xanthan, but there is seemingly no effect of acetylation on polytrimer xanthan viscosity. The further study of these materials should provide insight into the relationship between xanthan structure and rheological behavior.     

Synthesis and Fungicidal Activity of Diaryl 1,1 -Dichloroethyl-phosphonates

Non-Newtonian behavior and dynamic viscoelasticity of a series of aqueous mixed solutions of xanthan and locust bean gum were measured using a rheogoniometer, and the rheological properties were analysed. A gelation occurred in the mixture at the concentration of 0.2% total gums at room temperature. The flow curves of the mixture solutions showed a yield value and approximated to plastic behavior at 50°C. The maximum dynamic modulus was obtained when the mixing ratio of xanthan to locust bean gum was 1:2, while comparable high moduli were also obtained in the mixing ratio of 1: 3 or 1:4. A mixture of deacetylated xanthan and locust bean gum showed the highest dynamic modulus, about two times that of the mixture of native or Na-form xanthan. The dynamic modulus of the mixtures decreased rapidly with increasing temperature. In contrast, the dynamic viscosity was scarcely changed during increasing temperature in the mixing ratio of 2: 1. The dynamic modulus was decreased by addition of urea (4.0 M), NaCl (0.1%) and MgCl₂. We concluded that the intermolecular interaction between xanthan and locust bean gum might occur between the side chains of the former and backbone of the latter, as in a lock-and-key effect.     

Inter-Grade and Inter-Batch Variability of Sodium Alginate Used in Alginate-Based Matrix Tablets

The purpose of this study is to characterize the inter-grade and inter-batch variability of sodium alginate used in the formulation of matrix tablets. Four different grades and three batches of one grade of sodium alginate were used to prepare matrix tablets. Swelling, erosion, and drug release tests of sodium alginate matrix tablets were conducted in a USP dissolution apparatus. Substantial differences in swelling and erosion behavior of sodium alginate matrix tablets were evident among different viscosity grades. Even different batches of the same grade exhibit substantial differences in the swelling and erosion behavior of their matrix tablets. The erosion behavior of sodium alginate matrix tablets can be partly explained by their rheological properties (both apparent viscosity and viscoelasticity) in solution. Sodium alginate with higher apparent viscosity and viscoelasticity in solution show slower erosion rate and higher swelling rate. Compacts prepared from grades or batches with higher viscosity and higher viscoelasticity show slower drug release. For grades or batches with similar apparent viscosities, apparent viscosities of sodium alginate solution at low concentration alone are not sufficient to predict the functionality of sodium alginate in matrix tablets. Viscoelastic properties of sodium alginate solutions at one high concentration corresponding to the polymer gel state, may be suitable indicia of the extended release behavior of sodium alginate matrix tablets.     

Relationship between the Rheological Properties of Thickener Solutions and Their Velocity through the Pharynx as Measured by the Ultrasonic Pulse Doppler Method

The dependence of the dynamic viscoelastic parameters of carboxymethylcellulose (CMC), xanthan gum, and guar gum solutions on the angular frequency (ω) was compared with that of their viscosity (μ) on the shear rate (γ). In addition, the effect of these rheological properties on the maximum velocity through the pharynx, V _max, as measured by the ultrasonic pulse Doppler method, was investigated. The CMC and guar gum solutions examined were taken as a dilute solution and a true polymer solution, respectively. The xanthan gum solution was taken as a weak gel above 0.5% and a true polymer solution below 0.2%. The maximum velocity, V _max, of the thickener solutions correlated well with μ, the dynamic viscosity η′, and the complex viscosity η^*, especially those measured at γ or ω of 20–30 s^?1 (or rad/s) and above, suggesting that μ, η′, and η^* are suitable indexes for care foods of the liquid type for dysphagic patients.     

Guar Gum,Xanthan Gum,and HPMC Can Define Release Mechanisms and Sustain Release of Propranolol Hydrochloride

The objectives were to characterize propranolol hydrochloride-loaded matrix tablets using guar gum, xanthan gum, and hydroxypropylmethylcellulose (HPMC) as rate-retarding polymers. Tablets were prepared by wet granulation using these polymers alone and in combination, and physical properties of the granules and tablets were studied. Drug release was evaluated in simulated gastric and intestinal media. Rugged tablets with appropriate physical properties were obtained. Empirical and semi-empirical models were fit to release data to elucidate release mechanisms. Guar gum alone was unable to control drug release until a 1:3 drug/gum ratio, where the release pattern matched a Higuchi profile. Matrix tablets incorporating HPMC provided near zero-order release over 12 h and erosion was a contributing mechanism. Combinations of HPMC with guar or xanthan gum resulted in a Higuchi release profile, revealing the dominance of the high viscosity gel formed by HPMC. As the single rate-retarding polymer, xanthan gum retarded release over 24 h and the Higuchi model best fit the data. When mixed with guar gum, at 10% or 20% xanthan levels, xanthan gum was unable to control release. However, tablets containing 30% guar gum and 30% xanthan gum behaved as if xanthan gum was the sole rate-retarding gum and drug was released by Fickian diffusion. Release profiles from certain tablets match 12-h literature profiles and the 24-h profile of Inderal^® LA. The results confirm that guar gum, xanthan gum, and HPMC can be used for the successful preparation of sustained release oral propranolol hydrochoride tablets.     

Revisiting the conformation of xanthan and the effect of industrially relevant treatments

The structure and conformation of xanthan in aqueous solution following various processing treatments typically encountered in its application were investigated in this study. Treatments such as heating, autoclaving, high pressure homogenisation and irradiation were subjected to the same sample. Parameters such as weight average molecular weight (M(w)), polydispersity index, root mean square radius of gyration, intrinsic viscosity and Huggins constant were used to monitor the effect of these treatments. Additionally, we have quantified the mass recovery of samples examined by gel permeation chromatography and light scattering to properly account for all fractions present in xanthan solutions. Atomic force microscopy (AFM) images together with height measurements confirmed that xanthan conformation is double helical ordered renatured state (pre-heat treated by the manufacturer) in dilute solution conditions and random coil conformation in very dilute solution. The ordered (renatured) conformation is shown to have partially molten double helix, with more flexibility than the perfectly ordered native double helix. Heat treatment for 2h at 85°C reduces the M(w) of xanthan to half its initial value, and mass recovery measurements indicate that it completely overcomes its associative nature. Thermally treated xanthan solution in the dilute region leads to an order-disorder transition, as determined by contour length per unit mass. Similarly, irradiation of xanthan solution results in an order-disorder transition together with the production of single strand low molecular weight molecules. Autoclaving and high pressure homogenisation treatments cause degradation of xanthan. The results from treated xanthan solutions following high pressure homogenisation and irradiation confirm that xanthan does not reassociate. A revised summary of xanthan conformation in solution together with schematic models following the various treatments are proposed.     

Xanthan gum production under several operational conditions: molecular structure and rheological properties*

Xanthan gum production under several operational conditions has been studied. Temperature, initial nitrogen concentration and oxygen mass transfer rate have been changed and average molecular weight, pyruvilation and acetylation degree of xanthan produced have been measured in order to know the influence of these variables on the synthesised xanthan molecular structure. Also, xanthan gum solution viscosity has been measured, and rheological properties of the solutions have been related to molecular structure and operational conditions. The Casson model has been employed to describe the rheological behaviour. The parameter values of the Casson model, tau(0) and K(c), have been obtained for each polysaccharide synthesised under different operational conditions. Both pyruvilation and acetylation degrees and average molecular weight of xanthan increase with fermentation time at any operating conditions. Xanthan molecules with the highest average molecular weight have been obtained at 25 degrees C. Nevertheless, at this temperature acetate and pyruvate radical concentration are lowest. Nitrogen concentration in broth does not show any clear influence over xanthan average molecular weight, although with high nitrogen source concentration xanthan with low pyruvilation degree is produced.     

改善吞咽功能食品增稠剂的研究

为了提供一种适合老年吞咽障碍患者使用的增稠剂,以黄原胶和罗望子胶及麦芽糊精为原料,粘度及溶解时间为指标,采用单因素实验和正交实验相结合的方法确定胶体最适的复配比例。结果表明:复配后的胶体粘度均大于单一胶体的粘度,且三种胶体复配后的溶解速度得到了显著地提高。黄原胶、罗望子胶和麦芽糊精的最适复配比例为3∶1∶30,粘度为611mPa·s,溶解时间为3min。随后通过流变仪对复配溶液的流变特性及粘度进行分析验证。最后将最适配方的增稠剂与市面上具有代表性的国内外增稠剂进行对比,表明该配方的增稠剂不仅具有成本低及速溶的优势,还能应用于医学钡餐造影。     

Modeling the physicochemical properties of orange beverage emulsion as function of main emulsion components using response surface methodology

The effect of main beverage emulsion components namely Arabic gum (7–13% w/w), xanthan gum (0.1–0.3% w/w) and orange oil (6–10% w/w) on physicochemical properties of orange beverage emulsion was determined by using a three-factor central composite design (CCD). The reduced models with high R² (?0.80) values and non significant (p > .05) lack of fit were significantly (p < .05) fitted to the experimental data, thus ensuring a satisfactory fitness of the regression models relating the response to independent variables. The quadratic effect of xanthan gum had a significant (p < .05) term in all reduced models. The independent variables had the most significant (p < .05) effect on turbidity loss rate and viscosity ratio. The overall optimum region resulted in the desirable orange beverage emulsion was predicted at a combined level of 13% (w/w) Arabic gum, 0.3% (w/w) xanthan gum and 10% (w/w) orange oil.     

Sources and methods of manufacturing xanthan by fermentation of various carbon sources

Xanthan gum, an anionic polysaccharide with an exceptionally high molecular weight, is produced by the bacterium Xanthomonas sp. It is a versatile compound that has been utilized in various industries for decades. Xanthan gum was the second exopolysaccharide to be commercially produced, following dextran. In 1969, the US Food and Drug Administration (FDA) approved xanthan gum for use in the food and pharmaceutical industries. The food industry values xanthan gum for its exceptional rheological properties, which make it a popular thickening agent in many products. Meanwhile, the cosmetics industry capitalizes on xanthan gum's ability to form stable emulsions. The industrial production process of xanthan gum involves fermenting Xanthomonas in a medium that contains glucose, sucrose, starch, etc. as a substrate and other necessary nutrients to facilitate growth. This is achieved through batch fermentation under optimal conditions. However, the increasing costs of glucose in recent years have made the production of xanthan economically unviable. Therefore, many researchers have investigated alternative, cost-effective substrates for xanthan production, using various modified and unmodified raw materials. The objective of this analysis is to investigate how utilizing different raw materials can improve the cost-efficient production of xanthan gum.     

Impact of the extrusion process on xanthan gum behaviour

Processing xanthan gum by extrusion and subsequent drying produces a biopolymer showing particulate, rather than molecular behaviour in aqueous solution. This form of xanthan disperses very readily to give a viscosity that is strongly dependent on salt concentration. On heating above the temperature of the order-disorder transition as determined by calorimetry, there is a viscosity transition that is indicative of the irreversible loss of the particulate structure. It is suggested that the extrusion process melts and aligns xanthan macromolecules. On cooling reordering will occur but in the highly concentrated environment in the extruder ( approximately 45% water w/w), inter-molecular association between neighbouring macromolecules cannot proceed to completion due to kinetic trapping. As a consequence a network structure is created maintained by associations involving ordered regions. A xanthan solution can be prepared from this particulate material by dispersing and subsequent heating far more readily than can be achieved with non-processed xanthan.     

Some chemical and physical properties of extracellular polysaccharides produced by Butyrivibrio fibrisolvens strains

Most strains of Butyrivibrio fibrisolvens are known to produce extracellular polysaccharides (EPs). However, the rheological and functional properties of these EPs have not been determined. Initially, 26 strains of Butyrivibrio were screened for EP yield and apparent viscosities of cell-free supernatants. Yields ranged from less than 1.0 to 16.3 mg per 100 mg of glucose added to the culture. Viscosities ranged from 0.71 to 5.44 mPa.s. Five strains (CF2d, CF3, CF3a, CE51, and H10b) were chosen for further screening. The apparent viscosity of the EP from each of these strains decreased by only 50 to 60% when the shear rate was increased from 20 to 1,000 s-1. Strain CE51 produced the EP having the highest solution viscosity. A detailed comparison of shear dependency of the EP from strain CF3 with xanthan gum showed that this EP was less shear sensitive than xanthan gum and, at a shear rate of 1,000 s-1, more viscous. EPs from strains CF3 and H10b were soluble over a wide range of pH (1 to 13) in 80% (vol/vol) ethanol-water or in 1% (wt/vol) salt solutions. The pH of 1% EP solutions was between 4.5 and 5.5. Addition of acid increased solution viscosities, whereas addition of base decreased viscosity. EPs from strains CF3, CE51, and H10b displayed qualitatively similar infrared spectra. Calcium and sodium were the most abundant minerals in the three EPs. The amounts of magnesium, calcium, and iron varied considerably among the EPs, but the potassium contents remained relatively constant.     

Some chemical and physical properties of extracellular polysaccharides produced by Butyrivibrio fibrisolvens strains.

Most strains of Butyrivibrio fibrisolvens are known to produce extracellular polysaccharides (EPs). However, the rheological and functional properties of these EPs have not been determined. Initially, 26 strains of Butyrivibrio were screened for EP yield and apparent viscosities of cell-free supernatants. Yields ranged from less than 1.0 to 16.3 mg per 100 mg of glucose added to the culture. Viscosities ranged from 0.71 to 5.44 mPa.s. Five strains (CF2d, CF3, CF3a, CE51, and H10b) were chosen for further screening. The apparent viscosity of the EP from each of these strains decreased by only 50 to 60% when the shear rate was increased from 20 to 1,000 s-1. Strain CE51 produced the EP having the highest solution viscosity. A detailed comparison of shear dependency of the EP from strain CF3 with xanthan gum showed that this EP was less shear sensitive than xanthan gum and, at a shear rate of 1,000 s-1, more viscous. EPs from strains CF3 and H10b were soluble over a wide range of pH (1 to 13) in 80% (vol/vol) ethanol-water or in 1% (wt/vol) salt solutions. The pH of 1% EP solutions was between 4.5 and 5.5. Addition of acid increased solution viscosities, whereas addition of base decreased viscosity. EPs from strains CF3, CE51, and H10b displayed qualitatively similar infrared spectra. Calcium and sodium were the most abundant minerals in the three EPs. The amounts of magnesium, calcium, and iron varied considerably among the EPs, but the potassium contents remained relatively constant.     

Valorisation of chicken feathers for xanthan gum production using Xanthomonas campestris MO-03

Xanthan gum is an important commercial polysaccharide produced by Xanthomonas species. In this study, xanthan production was investigated using a local isolate of Xanthomonas campestris MO-03 in medium containing various concentrations of chicken feather peptone (CFP) as an enhancer substrate. CFP was produced with a chemical process and its chemical composition was determined. The addition of CFP (1–8?g/l) increased the conversion of sugar to xanthan gum in comparison with the control medium, which did not contain additional supplements. The highest xanthan production (24.45?g/l) was found at the 6?g/l CFP containing control medium in 54?h. This value was 1.73 fold higher than that of control medium (14.12?g/l). Moreover, addition of CFP improved the composition of xanthan gum; the pyruvate content of xanthan was 3.86% (w/w), higher than that of the control (2.2%, w/w). The xanthan gum yield was also influenced by the type of organic nitrogen sources. As a conclusion, CFP was found to be a suitable substrate for xanthan gum production.     

Yield stress components of waxy corn starch–xanthan mixtures: Effect of xanthan concentration and different starches

Yield stress of 6% (w/w) waxy maize (WXM), cross-linked waxy maize (CLWM), and cold water swelling (CWS) starches in xanthan gum dispersions: 0%, 0.35%, 0.50%, 0.70%, and 1.0% was measured with the vane method at an apparent shear rate of 0.05 s⁻¹. The intrinsic viscosity of the xanthan gum was determined to be: 112.3 dL/g in distilled water at 25 °C. Values of the static (σ_0s) and dynamic (σ_0d) yield stress of each dispersion were measured before and after breaking down its structure under continuous shear, respectively. The WXM and CWS starches exhibited synergistic behavior, whereas the CLWM starch showed antagonistic effect with xanthan gum. The difference (σ_0s − σ_0d) was the stress required to break the inter-particle bonding (σ_b). The contributions of the viscous (σ_v) and network (σ_n) components were estimated from an energy balance model. In general, values of σ_b of the starch–xanthan gum dispersions decreased and those of σ_n increased with increase in xanthan gum concentration.     

An anionic galactomannan polysaccharide gum from a newly-isolated lactose-utilizing bacterium. I. Strain description and gum characterization.

As part of an effort to obtain microorganisms able to produce polysaccharide gums from whey and whey permeate, soil samples from farm fields regularly treated with whey were screened for bacteria able to produce gums from lactose. The most promising organism isolated (ATCC 55046) is a facultative anaerobe, tentatively identified as a new Erwinia species on the basis of biochemical and morphological tests. The organism produces a polysaccharide gum from lactose and other sugars (herein named lactan gum) composed of mannose, galactose, and galacturonic acid with an approximate molar ratio of 5:3:2 and containing no organic acid modifying groups. The weight average molecular weight of the gum is approximately 7 x 10(6). Aqueous solutions of lactan gum exhibit shear-thinning and elastic flow behavior with an estimated power law model flow index of 0.26 at 1% (w/w) gum. The viscosity of aqueous 1% (w/w) lactan gum solutions is stable over a pH range of 2-11, being particularly stable in alkaline environments. Aqueous 1% (w/w) gum solutions at pH 5-11 show excellent thermostability, retaining at least 80% of the original viscosity after being heated to 121 degrees C for 15 min. These flow properties indicate potential industrial applications in food and nonfood products requiring a moderate degree of thickening, wet-end additives and coating agents for paper products, ceramics, detergents, and binders for building materials.     

Mode of action of a surfactant–polymer formulation to support performance of the entomopathogenic nematode Steinernema carpocapsae for control of diamondback moth larvae (Plutella xylostella)

The use of entomopathogenic nematodes on cabbage leaves against larvae of the diamondback moth (DBM) Plutella xylostella requires the addition of formulation adjuvants to achieve satisfying control. Without adjuvants nematodes settle in the tank mix of backpack sprayers causing uneven distribution. The polymers arabic and guar gum, alginate and xanthan were used in concentrations between 0.05 and 0.3% to retard sedimentation of Steinernema carpocapsae. Arabic gum had no effect, guar gum prevented sedimentation at 0.3% but the effect dropped significantly at lower concentration. At 0.05%, xanthan prevented nematode sedimentation better than alginate. Deposition of nematodes on the leaves was significantly increased by the addition of any of the polymers. Spraying nematodes on leaves with an inclination of 45° without the addition of any formulation resulted in 70% run-off. Adding 0.2% alginate or xanthan reduced the losses to <20%. The use of a surfactant–polymer formulation significantly reduced defoliation by DBM larvae. Visual examinations provided evidence that nematodes are not ingested by DBM larvae. Invasion of S. carpocapsae is an active process via the anus. The function of the formulation is not to prolong nematode survival, but to provide environmental conditions which enable rapid invasion of the nematodes. Nematode performance was improved by selection of the best surfactant in combination with xanthan and by optimisation of the concentrations of the surfactant Rimulgan® and the polymer xanthan. The best control results were achieved with Rimulgan® at 0.3% together with 0.3% xanthan, causing DBM mortality of >90% at 80% relative humidity and >70% at 60%. The formulation lowered the LC₅₀ from 12 to 1 nematode/larva. The viscosity of the surfactant–polymer formulations correlated well with nematode efficacy, prevention of sedimentation and adherence to the leave. This physical parameter can therefore be recommended for improvement of nematode formulations to be used for foliar application against DBM.