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.     

Relevance of Rheological Properties of Sodium Alginate in Solution to Calcium Alginate Gel Properties

The purpose of this study is to determine whether sodium alginate solutions’ rheological parameters are meaningful relative to sodium alginate’s use in the formulation of calcium alginate gels. Calcium alginate gels were prepared from six different grades of sodium alginate (FMC Biopolymer), one of which was available in ten batches. Cylindrical gel samples were prepared from each of the gels and subjected to compression to fracture on an Instron Universal Testing Machine, equipped with a 1-kN load cell, at a cross-head speed of 120 mm/min. Among the grades with similar % G, (grades 1, 3, and 4), there is a significant correlation between deformation work (L _E) and apparent viscosity (η _app). However, the results for the partial correlation analysis for all six grades of sodium alginate show that L _E is significantly correlated with % G, but not with the rheological properties of the sodium alginate solutions. Studies of the ten batches of one grade of sodium alginate show that η _app of their solutions did not correlate with L _E while tan δ was significantly, but minimally, correlated to L _E. These results suggest that other factors—polydispersity and the randomness of guluronic acid sequencing—are likely to influence the mechanical properties of the resultant gels. In summary, the rheological properties of solutions for different grades of sodium alginate are not indicative of the resultant gel properties. Inter-batch differences in the rheological behavior for one specific grade of sodium alginate were insufficient to predict the corresponding calcium alginate gel’s mechanical properties.     

Pullulan-sodium alginate based edible films: Rheological properties of film forming solutions

Rheological properties of pullulan, sodium alginate and blend solutions were studied at 20 °C, using steady shear and dynamic oscillatory measurements. The intrinsic viscosity of pure sodium alginate solution was 7.340 dl/g, which was much higher than that of pure pullulan (0.436 dl/g). Pure pullulan solution showed Newtonian behavior between 0.1 and 100 s⁻¹ shear rate range. However, increasing sodium alginate concentration in pullulan-alginate blend solution led to a shear-thinning behavior. The effect of temperature on viscosities of all solutions was well-described by Arrhenius equation. Results from dynamical frequency sweep showed that pure sodium alginate and blend solutions at 4% (w/w) polymer concentration were viscoelastic liquid, whereas the pure pullulan exhibited Newtonian behavior. The mechanical properties of pure sodium alginate and pullulan-alginate mixture were analyzed using the generalized Maxwell model and their relaxation spectra were determined. Correlation between dynamic and steady-shear viscosity was analyzed with the empirical Cox-Merz rule.     

Encapsulation of Ketoprofen and Ketoprofen Lysinate by Prilling for Controlled Drug Release

In this paper, ketoprofen and ketoprofen lysinate were used as model drugs in order to investigate release profiles of poorly soluble and very soluble drug from sodium alginate beads manufactured by prilling. The effect of polymer concentration, viscosity, and drug/polymer ratio on bead micromeritics and drug release rate was studied. Ketoprofen and ketoprofen lysinate loaded alginate beads were obtained in a very narrow dimensional range when the Cross model was used to set prilling operative conditions. Size distribution of alginate beads in the hydrated state was strongly dependent on viscosity of drug/polymer solutions and frequency of the vibration. The release kinetics of the drugs showed that drug release rate was related with alginate concentration and solubility of the drug. Alginate solutions with concentration higher than 0.50% (w/w) were suitable to prepare ketoprofen gastro-resistant formulation, while for ketoprofen lysinate alginate, concentration should be increased to 1.50% (w/w) in order to retain the drug in gastric environment. Differential scanning calorimetry thermograms and Fourier transform infrared analyses of drug-loaded alginate beads indicated complex chemical interactions between carboxyl groups of the drug and polymer matrix in drug-loaded beads that contribute to the differences in release profile between ketoprofen and ketoprofen lysinate. Total release of the drugs in intestinal medium was dependent on the solubility of the drug and was achieved between 4 and 6 h.     

<Emphasis Type="Italic">In Situ</Emphasis> Gelling Gelrite/Alginate Formulations as Vehicles for Ophthalmic Drug Delivery

The objective of this study was to develop an ion-activated in situ gelling vehicle for ophthalmic delivery of matrine. The rheological properties of polymer solutions, including Gelrite, alginate, and Gelrite/alginate solution, were evaluated. In addition, the effect of formulation characteristics on in vitro release and in vivo precorneal drug kinetic of matrine was investigated. It was found that the optimum concentration of Gelrite solution for the in situ gel-forming delivery systems was 0.3% (w/w) and that for alginate solution was 1.4% (w/w). The mixture of 0.2% Gelrite and 0.6% alginate solutions showed a significant enhancement in gel strength at physiological condition. On the basis of the in vitro results, the Gelrite formulations of matrine-containing alginate released the drug most slowly. For each tested polymer solution, the concentration of matrine in the precorneal area was higher than that of matrine-containing simulated tear fluid (STF) almost at each time point (p < 0.05). The area under the curve of formulation 16 (0.2%Gelrite/0.6%alginate) was 4.65 times greater than that of containing matrine STF. Both the in vitro release and in vivo pharmacological studies indicated that the Gelrite/alginate solution had the better ability to retain drug than the Gelrite or alginate solutions alone. The tested formulation was found to be almost non-irritant in the ocular irritancy test. The overall results of this study revealed that the Gelrite/alginate mixture can be used as an in situ gelling vehicle to enhance ocular retention.     

Preparation and <Emphasis Type="Italic">In Vitro</Emphasis>/<Emphasis Type="Italic">In Vivo</Emphasis> Evaluation of Microparticle Formulations Containing Meloxicam

In this study, we have formulated chitosan-coated sodium alginate microparticles containing meloxicam (MLX) and aimed to investigate the correlation between in vitro release and in vivo absorbed percentages of meloxicam. The microparticle formulations were prepared by orifice ionic gelation method with two different sodium alginate concentrations, as 1% and 2% (w/v), in order to provide different release rates. Additionally, an oral solution containing 15 mg of meloxicam was administered as the reference solution for evaluation of in vitro/in vivo correlation (ivivc). Following in vitro characterization, plasma levels of MLX and pharmacokinetic parameters [elimination half-life (t _1/2), maximum plasma concentration (C _max), time for C _max (t _max)] after oral administration to New Zealand rabbits were determined. Area under plasma concentration–time curve (AUC_0–∞) was calculated by using trapezoidal method. A linear regression was investigated between released% (in vitro) and absorbed% (in vivo) with a model-independent deconvolution approach. As a result, increase in sodium alginate content lengthened in vitro release time and in vivo t _max value. In addition, for ivivc, linear regression equations with r ² values of 0.8563 and 0.9402 were obtained for microparticles containing 1% and 2% (w/v) sodium alginate, respectively. Lower prediction error for 2% sodium alginate formulations (7.419 ± 4.068) compared to 1% sodium alginate formulations (9.458 ± 5.106) indicated a more precise ivivc for 2% sodium alginate formulation.     

Sustained Release of a Water-Soluble Drug from Alginate Matrix Tablets Prepared by Wet Granulation Method

Alginate matrix tablet of diltiazem hydrochloride (DTZ), a water-soluble drug, was prepared using sodium alginate (SAL) and calcium gluconate (CG) by the conventional wet granulation method for sustained release of the drug. The effect of formulation variables like SAL/CG ratio, drug load, microenvironmental pH modulator, and processing variable like compression force on the extent of drug release was examined. The tablets prepared with 1:2 w/w ratio of SAL/CG produced the most sustained release of the drug extending up to 13.5 h. Above and below this ratio, the drug release was faster. The drug load and the hardness of the tablets produced minimal variation in drug release. The addition of alkaline or acidic microenvironmental modulators did not extend the release; instead, these excipients produced somewhat faster release of diltiazem. This study revealed that proper selection of SAL/CG ratio is important to produce alginate matrix tablet by wet granulation method for sustained release of DTZ.     

Phosphomannose-isomerase (<Emphasis Type="Italic">pmi</Emphasis>) gene as a selectable marker for <Emphasis Type="Italic">Agrobacterium</Emphasis>-mediated transformation of rapeseed

Nodal segments (4 ± 1 mm long) of Hibiscus moscheutos (hardy hibiscus) were excised from in vitro proliferating microshoots and utilized to evaluate initial factors involved in bulk alginate encapsulation. The factors evaluated were; storage vessel type, volume and multiple rinse effects of CaCl₂ solutions, and sodium alginate concentrations (2.5, 2.75, 3.0 or 3.25%) for bulk alginate encapsulation. Results indicate that vessels utilized for bulk alginate encapsulation should have a lower base area (L × W) to height ratio to reduce the amount of alginate matrix shrinkage resulting in exposure of nodal segments. Increased volumes and multiple 50 mM CaCl₂ solution rinses did not have an effect on alginate solidification. Shoot length, root number, and root length significantly decreased in a linear manner from nodal explants stored for 4 weeks with increasing concentrations of sodium alginate. This research suggests an innovative technique for alginate encapsulation of H. moscheutos utilizing bulk methods as an alternative to single bead alginate encapsulation.     

Inter- and Intra-Manufacturer Variability in Pharmaceutical Grades and Lots of Xanthan Gum

A pharmaceutical formulation typically contains one or more excipients in addition to the active pharmaceutical ingredient(s). Though excipients have been considered inert components of a formulation, variability in their properties has been shown to affect the performance of drug dosage forms and delivery systems. This study investigates the inter- and intra-manufacturer variability among different NF grades and lots of xanthan gum made by two manufacturers. As many formulators rely on compendial standards to monitor and control the variability of excipients, this study focuses on the adequacy of the NF specifications, in particular the viscosity specification, to discern the variability in solution properties of different pharmaceutical grades and lots of xanthan gum. All the grades and lots in this study were NF grade materials. Xanthan gum solutions were prepared in accordance with NF test methodology and were rheologically evaluated using a rotational rheometer. Both steady shear measurements and small amplitude oscillatory measurements were carried out on 1% w/w xanthan gum solutions. Results showed significant inter- and intra-manufacturer variability among the NF grades and lots of xanthan gum that was not reflected in the NF viscosity test specifications.     

The invasive brown seaweed Sargassum muticum as new resource for alginate in Morocco: Spectroscopic and rheological characterization

The Japanese brown seaweed Sargassum muticum, recently invaded several shorelines worldwide including the Atlantic coast of Morocco with large well‐established populations. Within the framework of a sustainable strategy to control this invasive seaweed, we report on extraction yield, spectroscopic characterization and rheological properties of alginate, a commercially valuable colloid, from harvested biomass of S. muticum. Extraction yield was about 25.6% on dry weight basis. Infrared spectroscopy analysis shows that the obtained Fourier transform infrared spectra of the extracted biopolymer exhibit strong similarities with that of the commercial alginate. Furthermore, Proton nuclear magnetic resonance spectroscopy revealed that S. muticum alginate has almost equal amounts of β‐D‐mannuronic acid (M; 49%) and α‐L‐guluronic acid (G; 51%) with an M/G ratio of 1.04 and a high content of heteropolymeric MG GM diads suggesting a sequence distribution of an alternated polymer type. Rheological measurements were performed at different sodium alginate concentrations, temperatures and shear rates. The hydrocolloid exhibited pseudoplastic behavior and showed shear thinning, particularly at high solution concentration and low temperature which is consistent with the rheological behavior reported for commercial alginates. Considering the abundance of S. muticum in the Northwestern Atlantic coast of Morocco and the quality of the extracted hydrogel, this invasive species could be considered as a potential source of alginates.     

Short communication: Methylparathion degradation by Pseudomonas sp. A3 immobilized in sodium alginate beads

An organophosphate-degrading soil isolate of Pseudomonas sp. A3, immobilized at 5% (wet wt/v) cell mass in 3% (w/v) sodium alginate beads, detoxified 99% of 1 mm methylparathion in 48 h. The beads were re-usable for five batches, the sixth batch only giving 73% methylparathion removal.     

Increasing the stability of immobilizedLactococcus lactis cultures stored at 4 °C

Summary Immobilized cell technology was used to prepare concentrated cultures ofLactococcus lactis that lost only 22% of viability over a 30-day storage period at 4°C. Concentrated cultures ofL lactis CRA-1 were immobilized in calcium alginate beads and added to glycerol, NaCl or sucrose-NaCl solutions in order to obtain a_w readings ranging from 0.91 to 0.97. The suspensions were subsequently placed at 4°C and viability (CFU g^–1 of bead) was followed during storage. Viability losses were high at a_w readings of 0.95 and 0.97 and pH dropped significantly (up to one unit) in the unbuffered solutions. Addition of 1% soytone or glycerophosphate helphed stabilize pH, and a beneficial effect on viability during storage was observed in the glycerol-soytone mix when the beads were added to the conservation solutions immediately following immobilization. When beads were added to the conservation solution immediately following immobilization, a 70% drop in cell counts occurred during the first 5 days of incubation. Dipping theL lactis-carrying beads in milk for 2h before mixing with the glycerolsoytone 0.93 a_w solution reduced this initial 5-day viability loss. Cultures grown in the alginate beads also had good stability in the 0.93 a_w glycerol-soytone solution, where 78% of the population was viable after 30 days at 4°C. The process could be used to store immobilized cells at a processing plant, or by suppliers of lactic starters who wish to ship cultures without freezing or drying.     

Modulation of Tramadol Release from a Hydrophobic Matrix: Implications of Formulations and Processing Variables

In the present investigation, hydrogenated cottonseed oil (HCSO) was evaluated as a sustained release matrix for a freely soluble drug, tramadol. Hydrophobic matrix tablets of tramadol, was evaluated by compression of physical mixture of drug and wax, dispersion of drug in HCSO by hot fusion or solubilisation techniques. The method of preparation of tablet had a significant effect on drug release with higher release observed from direct compression matrices and slower release from matrix prepared by dispersion (hot-fused matrices). Influence of addition of hydroxypropylmethyl cellulose, sodium carboxymethyl cellulose, polyethylene glycol 4000 and surfactants like sodium lauryl sulphate and polysorbate 20 to HCSO matrix on drug release was investigated. The added excipients exhibited a propensity to enhance drug release from the HCSO matrix. NaCMC was effective at a lower ratio (<10% w/w) and when incorporated at higher level made HCSO matrix to erode and disintegrate in a short period.     

RETRACTED ARTICLE: The Influence of Sodium Hyaluronate, <Emphasis Type="SmallCaps">l</Emphasis>-Leucine and Sodium Taurocholate on the Nebulization of Aqueous Betamethasone-17-Valerate Suspensions

The purpose of this research was to evaluate the variables that are suggested to influence the adsorption of the hydrophilic hyaluronic acid (HA) onto the surface of the hydrophobic betamethasone-17-valerate (BV) particles in order to formulate a nebulizable suspension. The adsorption of HA from aqueous solutions (0.04% to 0.16%, w/v) to a fixed BV concentration (0.04%, w/v) under different experimental conditions, was investigated. The method of preparation of HA-BV suspensions involved suspending BV particles either in the hydrated HA solution (method 1) or in water followed by addition of solid HA (method 2). Other variables like the time required for the adsorption to complete and temperature at which adsorption is carried out were studied. The nebulization of the suspensions was tested via an air jet nebulizer connected to a twin stage impinger. In order to improve the nebulization behavior of the optimized suspension, l-leucine or sodium taurocholate was incorporated in increasing concentrations (0.01–0.04%, w/v). The optimized suspension, having a nebulization efficiency of 33.75%, was achieved following the adsorption of HA (0.1%, w/v) onto BV particles adopting method 2 of preparation and extending for three days at 4 °C. Incorporation of either l-leucine or sodium taurocholate significantly decreased the aggregate size of the optimized suspension and consequently caused significant increases in the nebulization efficiency to reach 46.87% and 56.25%, respectively. An erratum to this article is available at .     

Physicochemical and Rheological Characterization of Gum Tragacanth Exudates from Six Species of Iranian <Emphasis Type="Italic">Astragalus</Emphasis>

The flow behavior of six species of Iranian gum tragacanth dispersions was investigated at different temperatures and ionic strengths, within a concentration range (0.05–1.5% w/w) using a controlled shear rate rheometer. The steady shear measurements showed that all of the gum dispersions had shear-thinning natures. The power law model was used to describe the rheological properties of dispersions and Arrhenius model was used to evaluate the temperature effect. Composition analysis, surface tension measurement, particle size analysis, and color measurement of all the species were also carried out. The results indicated that the six species of gum tragacanth being studied in this paper exhibited significantly different physicochemical properties. Therefore, various species of gum tragacanth can be used instead of different hydrocolloids in a wide range of applications.     

Microencapsulation by Spray Coagulation of Diltiazem HCl in Calcium Alginate-Coated Chitosan

The aim of this work was to develop a procedure for encapsulation of diltiazem HCl by spray coagulation. Factors affecting the formulations such as the effect of NaCl on the solubility of diltiazem in alginate solution, surface tension, pH, viscosity of the coagulation medium, and the effect of drug load on drug release were studied. The drug load was increased substantially from 10 up to 320 mg/mL by adding 1.2% w/v NaCl in 1% w/v alginate solution. More stable microcapsules were obtained at pH 4.6 (acetate buffer) than at a pH 2.8 (lactic acid), and the microencapsulation process was favored by the type of chitosan that produced low turbidity and viscosity in the coagulation medium. A dose of 50 mg/mL of diltiazem HCl, 1.2% w/v NaCl, and chitosan CS allowed higher amount of drug to be encapsulated. The high water solubility of diltiazem HCl leads to fast release from the microcapsules.     

Viscosity study of interactions between sodium alginate and CTAB in dilute solutions at different pH values

Interactions between anionic polyelectrolyte sodium alginate and the cationic surfactant cetytrimethylammonium bromide (CTAB) have been investigated by viscosity measurement techniques. The polymer–surfactant interactions are observed between alginate and CTAB at different pH in dilute solution. The results show that the rheological response of alginate dilute solutions is sensitive to a change of pH in the low pH range. The steady shear and intrinsic viscosity measurements reveal that the strong association between alginate and CTAB by electrostatic attraction above pH 5.0. However, as the pH value of solution decrease from 5.0 to 3.0, the strong association between alginate and CTAB is affected by not only electrostatic attraction but also hydrophobic interaction.     

Extraction and characterisation of alginate from brown seaweeds (Fucales,Phaeophyceae) collected from Port Dickson,Peninsular Malaysia

Four species of brown seaweeds, namely Sargassum baccularia, Sargassum binderi, Sargassum siliquosum and Turbinaria conoides, harvested from Port Dickson, Negeri Sembilan, Malaysia were analysed for ash content, alginate yield and alginate properties. Seaweeds calcined at 450°C were found to have low amount of non-combustible residue as these were not contaminated by calcareous animals. Alginate was extracted from these seaweeds by two methods: hot and cold. In the hot method, the storing time was 3 h and the processing temperature was 50°C, whilst in the cold method, the sample was stored overnight at room temperature. Higher yield of alginate was obtained by the hot method compared to the cold method, but alginate extracted by the cold method gave higher molecular weight. In the hot method, 49.9% of alginate was extracted from S. siliquosum, followed by T. conoides (41.4%), S. binderi (38.9%) and S. baccularia (26.7%). Alginate extracted from T. conoides has an average molecular weight, M _w, of 8.06 × 10⁵ g mol⁻¹, whereas alginate from S. siliquosum was the lowest in M _w (4.81 × 10⁵ g mol⁻¹) when the extraction was done at room temperature. Alginate extracted from S. baccularia was found to be very heat-sensitive. Its M _w has dropped more than 83%, from 7.52 × 10⁵ to 1.23 × 10⁵ g mol⁻¹, when the extraction temperature was raised. The effect of heat on the extent of depolymerisation of the alginate molecule of the other three brown seaweed species was less significant, with decrease in molecular weight ranging between 13% and 16%.     

Optical resolution and mechanism using enantioselective cellulose,sodium alginate and hydroxypropyl‐β‐cyclodextrin membranes

Chiral solid membranes of cellulose, sodium alginate, and hydroxypropyl‐β‐cyclodextrin were prepared for chiral dialysis separations. After optimizing the membrane material concentrations, the membrane preparation conditions and the feed concentrations, enantiomeric excesses of 89.1%, 42.6%, and 59.1% were obtained for mandelic acid on the cellulose membrane, p ‐hydroxy phenylglycine on the sodium alginate membrane, and p ‐hydroxy phenylglycine on the hydroxypropyl‐β‐cyclodextrin membrane, respectively. To study the optical resolution mechanism, chiral discrimination by membrane adsorption, solid phase extraction, membrane chromatography, high‐pressure liquid chromatography ultrafiltration were performed. All of the experimental results showed that the first adsorbed enantiomer was not the enantiomer that first permeated the membrane. The crystal structures of mandelic acid and p ‐hydroxy phenylglycine are the racematic compounds. We suggest that the chiral separation mechanism of the solid membrane is “adsorption – association – diffusion,” which is able to explain the optical resolution of the enantioselective membrane. This is also the first report in which solid membranes of sodium alginate and hydroxypropyl‐β‐cyclodextrin were used in the chiral separation of p ‐hydroxy phenylglycine.     

Effects of sodium alginate elicitation on secondary metabolites and antioxidant activity of safflower genotypes under in vitro salinity stress

The present study was aimed at investigating the effects of different concentrations of sodium alginate (NaAlg) (0.075 and 0.15% (w/v)) on the production of secondary metabolites (SMs) and antioxidant activity of seven safflower genotypes under in vitro salinity stress. The results showed that total phenolic content (TPC), total flavonoids (TFD), total flavonols (TFL), anthocyanin (Ant), total antioxidant capacity (TAC), phenylalanine ammonia-lyase (PAL), catalase (CAT) activity, and lipid peroxidation significantly increased under salinity stress consisting of the concentration of 1.5% (w/v) of NaCl, but callus growth traits decreased. The highest amount of TPC, Ant, and callus growth traits was observed under the elicitation of the sample with the concentration of 0.075(%) NaAlg under salinity stress, but the highest amount for TFD, TFL, CAT, PAL, and TAC was observed under elicitation of the sample with the concentration of 0.15% of NaAlg under salinity stress. This indicated the superiority of NaAlg for elicitation to increase SMs in safflower under salinity stress. Overall, the results showed that genotypes of Mex.22-191 and GE₆₂₉₁₈ could be processed to produce SMs by eliciting NaCl in safflower as an important medicinal plant at cellular level. A positive and significant correlation between CAT and TPC was observed and indicates that phenolic compounds are the major contributors to the antioxidant potential in safflower. This new elicitor introduced new ways to select and exploit the best NaAlg concentration to develop SMs that are of tremendous importance in terms of commercial purposes along with medical features in safflower at cellular level.