Development and evaluation of anti-reflux functional-oral suspension raft composed of sodium alginate-mung bean protein complex.

This study aimed to develop a sodium alginate (Na alginate) and mung bean protein (MBP) raft complex to improve gastric reflux symptoms. Na alginate and MBP complexes with different ratios (1:1, 2:1, and 3:1, respectively) were used for raft formulations through a wet Maillard reaction. Structural properties of raft strength, reflux resistance, intrinsic fluorescence emission spectroscopy, and Fourier transform infrared spectroscopy (FTIR) were investigated for rafts. The suspension 1:1 Na alginate/MBP with 0 h Maillard reaction time exhibited the lowest sedimentation volume among the suspensions. In contrast, 3:1 Na alginate/MBP with 6 h Maillard reaction time showed the highest sedimentation volume. Based on the results, the 3:1 Na alginate/MBP rafts had the best results, and the results were within acceptable limits. Functional properties, including antioxidant properties, the Helicobacter pylori inhibition assay, the pancreatic lipase inhibition assay, and angiotensin-converting enzyme (ACE) inhibition, were investigated for rafts. The Na alginate/MBP raft has similar characteristics to Gaviscon syrup and can be used for obesity, Helicobacter pylori infection, high blood pressure, and gastric reflux.

Alkaline deep eutectic solvents as novel and effective pretreatment media for hemicellulose dissociation and enzymatic hydrolysis enhancement.

In recent years, deep eutectic solvents (DESs) are used for enhancing the enzymatic digestibility and lignin fractionation in pretreatment, while hemicellulosic fraction receives scant attention. Herein, we report a novel approach of applying alkaline deep eutectic solvents (ADESs) for dissociating hemicelluloses from woody biomass. Among these ADESs, choline chloride-monoethanolamine (C-M) was the most efficacious medium for deconstructing the recalcitrant structure of poplar and 63.3% of hemicelluloses was obtained at 80 °C. Structure analysis showed that the ADESs-extracted hemicelluloses retained partial of O-acetyl groups. Different ADESs could be used to obtain hemicelluloses with various degrees of branching. Furthermore, the enzymatic digestibility of cellulose was significantly increased by 6.6 times compared to that of the untreated poplar under the optimum conditions (C-M, 140 °C). This work provides a view on the dissociation behavior of hemicelluloses during ADESs pretreatment, which would be beneficial for devising DESs toward effective fractionation and comprehensive utilization of biomass.

Tannylated Calcium Carbonate Materials with Antacid, Anti-Inflammatory, and Antioxidant Effects.

Calcium carbonate (CaCO3)-based materials have received notable attention for biomedical applications owing to their safety and beneficial characteristics, such as pH sensitivity, carbon dioxide (CO2) gas generation, and antacid properties. Herein, to additionally incorporate antioxidant and anti-inflammatory functions, we prepared tannylated CaCO3 (TA-CaCO3) materials using a simple reaction between tannic acid (TA), calcium (Ca2+), and carbonate (CO32-) ions. TA-CaCO3 synthesized at a molar ratio of 1:75 (TA:calcium chloride (CaCl2)/sodium carbonate (Na2CO3)) showed 3-6 µm particles, comprising small nanoparticles in a size range of 17-41 nm. The TA-CaCO3 materials could efficiently neutralize the acid solution and scavenge free radicals. In addition, these materials could significantly reduce the mRNA levels of pro-inflammatory factors and intracellular reactive oxygen species, and protect chondrocytes from toxic hydrogen peroxide conditions. Thus, in addition to their antacid property, the prepared TA-CaCO3 materials exert excellent antioxidant and anti-inflammatory effects through the introduction of TA molecules. Therefore, TA-CaCO3 materials can potentially be used to treat inflammatory cells or diseases.

Calcium Carbonate for Elemental Lead Ingestions: Effect of Alkalinization on Elemental Lead Solubility in a Simulated Gastric Environment.

INTRODUCTION: Acute ingestion of elemental lead foreign bodies has resulted in multiple pediatric deaths. Elemental lead is relatively insoluble at alkaline pH. Furthermore, calcium decreases lead absorption by interfering with the lead absorptive receptor. We hypothesize that alkalinization of gastric fluid with an oral calcium-containing agent, such as calcium carbonate, will decrease lead solubility, thus reducing the potential for systemic lead absorption and toxicity. METHODS: This was an in vitro controlled study. One lead sphere (00 buckshot, cast 30 days prior) was randomly placed in each of ten tubes containing 20 mL simulated gastric fluid, with five tubes having 500 mg calcium carbonate added at 20 min and 140 min. We measured the fluid pH and the lead concentrations hourly for 4 h. We compared the median amount of total lead liberated after 4 h between the two groups using the Mann-Whitney U test. RESULTS: The pH of the gastric fluid only tubes remained 1 at every measurement, and the pH of the gastric fluid + calcium carbonate tubes was 6 at every measurement. At hour 4, the total amount of lead liberated in the soluble fraction in the control group vs the calcium carbonate group was 850 vs 12.4 mcg (95% CI for absolute difference: 605-964 mcg; p = 0.0079). CONCLUSIONS: Calcium carbonate antacid alkalinizes gastric fluid pH and dramatically decreases the total amount of solubilized lead by 60-fold. This project lends foundational evidence to a low-cost, widely available, pre-hospital strategy to decrease lead absorption after acute elemental lead ingestions.

Antimicrobial Activity and Barrier Properties against UV Radiation of Alkaline and Enzymatically Treated Linen Woven Fabrics Coated with Inorganic Hybrid Material.

One of the directions of development in the textiles industry is the search for new technologies for producing modern multifunctional products. New solutions are sought to obtain materials that will protect humans against the harmful effects of the environment, including such factors as the activity of microorganisms and UV radiation. Products made of natural cellulose fibers are often used. In the case of this type of material, it is very important to perform appropriate pretreatment before subsequent technological processes. This treatment has the aim of removing impurities from the surface of the fibers, which results in the improvement of sorption properties and adhesion, leading directly to the better penetration of dyes and chemical modifiers into the structure of the materials. In this work, linen fabrics were subjected to a new, innovative treatment being a combination of bio-pretreatment using laccase from Cerrena unicolor and modification with CuO-SiO2 hybrid oxide microparticles by a dip-coating method. To compare the effect of alkaline or enzymatic pretreatment on the microstructure of the linen woven fabrics, SEM analysis was performed. The new textile products obtained after this combined process exhibit very good antimicrobial activity against Candida albicans, significant antibacterial activity against the Gram-negative Escherichia coli and the Gram-positive Staphylococcus aureus, as well as very good UV protection properties (ultraviolet protection factor (UPF) > 40). These innovative materials can be used especially for clothing or outdoor textiles for which resistance to microorganisms is required, as well as to protect people who are exposed to long-term, harmful effects of UV radiation.

Cutaneous Reactions to Aluminum.

: Cutaneous exposure to aluminum may occur via contact with metal items, medications, and personal care products. Despite the widespread use of aluminum, allergic contact dermatitis is relatively rare. Sensitization is often incidentally identified during patch testing with aluminum-based chambers. This article presents several cases along with a literature review summarizing prevalence and clinical manifestations of cutaneous reactions to aluminum, recommendations for patch testing, sources of aluminum, and reproducibility of aluminum allergy over time.

Chewable Antacid Tablets: Are Disintegration Tests Relevant?

A recently published FDA guidance on chewable tablets has addressed the quality attributes of this class of dosage forms. This study evaluated disintegration as a quality attribute for a number of commercially available chewable antacid tablets. Additionally, acid-neutralizing-capacity values were evaluated. A number of the products exhibited prolonged disintegration times-which were far longer than those of conventional immediate-release tablets. The mean disintegration times ranged from 6 to more than 60 min in distilled water and from 9 to over 60 min in 0.1 N HCl. The products with longer disintegration times had higher breaking force and tensile strength values. Despite the range in disintegration times, all products met the criteria for acid-neutralizing capacity. These results indicate a need for patients to be aware of the need to thoroughly chew antacid tablets upon administration. Given these considerations, disintegration testing would be a useful quality control test in evaluating these dosage forms as the implicit assumption by the manufacturer that patients will chew the product sufficiently may not be met in every case.

Pretreatment of willow using the alkaline-catalyzed sulfolane/water solution for high-purity and antioxidative lignin production.

In this study, an alkaline-catalyzed sulfolane/water solvent system was developed for isolating high-purity and antioxidative lignin from willow (Salix matsudana cv. Zhuliu). Optimization of the pretreatment conditions such as temperature, sulfolane/water ratio, and alkaline catalyst (NaOH) dosage were comprehensively investigated for effective lignin extraction from willow. The 44.4% of lignin was recovered from the biomass with 54% of delignification in 50/50 (w/w) sulfolane/water system at 170 °C. As the addition of the alkaline catalyst (NaOH) increased to 4%, the delignification yield was increased up to 94% with about 70% of lignin recovery yield. The recovered lignin was comparatively investigated with its control, milled wood lignin (MWL). The ß-O-4 linkages and phenolic hydroxyl were well preserved in the extracted lignin fractions with the sulfolane/water system. Furthermore, excellent radical scavenging ability was observed with the extracted lignins by sulfolane/water pretreatments owing to rich phenolic hydroxyl groups in the lignins. Hence, systematical investigation on the lignin properties and potential applications under sulfolane organosolv pretreatment would promote the utilization of lignin in biorefinery processes.

Analytical and pharmacological validation of the quantification of phenol red in a mouse model: An optimized method to evaluate expectorant drugs.

INTRODUCTION: The evaluation of expectorant activity has been extensively studied in murine models, involving the secretion of phenol red in the trachea or bronchus to estimate the secretory capacity of lower airway mucosa. However, differences in the experimental protocols of several studies evidenced the need of to standardize the quantification of phenol red in the bronchoalveolar fluid (BALF). METHODS: The analytical methodology for the quantification of phenol red in the BALF was optimized by investigation of pH influence, quantity of the alkali agent added and appropriate wavelength for quantification of phenol red by UV-VIS spectroscopy. Different phenol red suspensions (0.05, 0.5, 1.25, 2.5 and 5%) were prepared and administered intraperitoneally in mice at doses 5, 25, 50, 250 or 500 mg/kg. RESULTS: It was shown that phenol red should be used at dose 500 mg/kg and intraperitoneal administration should be performed from a suspension at 1.25% (w/v). Furthermore, the alkalinizing agent of choice would be NaOH (0.1 M). The pharmacological validation of the analytical method showed that ambroxol (30, 60 or 120 mg/kg), guaifenesin (100 mg/kg), NH4Cl (2000 mg/kg) or salbutamol (4 mg/kg) can be used as positive controls. DISCUSSION: The phenol red quantification in the BALF is a rapid and low cost assay for the discovery of new expectorant drugs. Thus, it was proposed a standardization of the analytical and pharmacological methods to ensure the reliability of BALF processing and reproducibility of phenol red quantification for data analysis.

Formulation development of sugar free antacid chewable tablets for diabetes induced acidity in patients.

Sugar free chewable tablets are considered to be desired medication for diabetic population having acid reflex problems. The main objective of this study is to develop a patient complaint tablet dosage form which is sugar free, chewable and easy to use. The formulation is designed for hyperglycemic and dysphasic patients along acidity or stomach ulcer. For manufacturing Aluminum Hydroxide (Kyowa Japan), Magnesium Hydroxide (Taurus chemicals India) Simethicone, Povidone (JRS pharma) Sorbitol powder, Magnesium stearate, Dilcalcium phosphate anhydrous, SSG (JRS pharma) and Aspartame were used. The granules formed by wet granulation method and tablets are compressed by rotary compression machine. The pre-formulation studies of granules (Angle of repose, Bulk/Tapped density, Carr's compressibility index and Hausner's ratio), uniformity of content (assay), acid neutralizing capacity, Identification by FTIR spectroscopy all are found within the limits as per USP specifications. All three formulation batches are stable under accelerated and ambient stability conditions for 6 months and 24 months respectively. The formulation development of sugar free oral chewable antacid tablet is pharmaceutically stable and can further analyze for safety and efficacy studies.

Rational Design of a Famotidine-Ibuprofen Coamorphous System: An Experimental and Theoretical Study.

Famotidine (FMT) and ibuprofen (IBU) were used as model drugs to obtain coamorphous systems, where the guanidine moiety of the antacid and the carboxylic group of the nonsteroidal anti-inflammatory drug could potentially participate in H-bonds leading to a given structural motif. The systems were prepared in 3:7, 1:1, and 7:3 FMT and IBU molar ratios, respectively. The latter two became amorphous after 180 min of comilling. FMT-IBU (1:1) exhibited a higher physical stability in assays at 4, 25, and 40 °C up to 60 days. Fourier transform infrared spectroscopy accounted for important modifications in the vibrational behavior of those functional groups, allowing us to ascribe the skill of 1:1 FMT-IBU for remaining amorphous to equimolar interactions between both components. Density functional theory calculations followed by quantum theory of atoms in molecules analysis were then conducted to support the presence of the expected FMT-IBU heterodimer with consequent formation of a R228 structural motif. The electron density (ρ) and its Laplacian (∇2ρ) values suggested a high strength of the specific intermolecular interactions. Molecular dynamics simulations to build an amorphous assembly, followed by radial distribution function analysis on the modeled phase were further employed. The results demonstrate that it is a feasible rational design of a coamorphous system, satisfactorily stabilized by molecular-level interactions leading to the expected motif.

Tablet Formulation of a Polymeric Solid Dispersion Containing Amorphous Alkalinized Telmisartan.

To overcome the poor dissolution of telmisartan (TMS) at weak acidic pH, amorphous alkalinized TMS (AAT) was prepared by introducing sodium hydroxide as a selective alkalizer. AAT-containing polymeric solid dispersions were prepared by a solvent evaporation method; these solid dispersions were AAT-PEG, AAT-PVP, AAT-POL, and AAT-SOL for the polymers of PEG 6000, PVP K30, Poloxamer 407, and Soluplus, respectively. The characteristics of the different formulations were observed by differential scanning calorimetry, powder X-ray diffraction, Fourier transform infrared spectroscopy, and scanning electron microscopy. To compare the supersaturation behavior, a dissolution test was performed at 37 ± 0.5 °C either in 900 ml (plain condition) or 500 ml (limited condition) of pH 6.8-simulated intestinal fluid used as a medium. AAT-SOL exhibited enhanced dissolution, indicating the probability of extended supersaturation in the limited condition. AAT-SOL was further formulated into a tablet by introducing other excipients, Vivapur 105 and Croscarmellose, as a binder and superdisintegrant, respectively, using a direct compression method. The selected AAT-SOL tablet was superior to Micardis (the reference product) in the aspect of supersaturation maintenance during dissolution in the limited condition, suggesting that it is a promising candidate for practical development that can replace the commercial product in the future.

Development of Functional or Medical Foods for Oral Administration of Insulin for Diabetes Treatment: Gastroprotective Edible Microgels.

Insulin and an antacid [Mg(OH)2] were co-encapsulated inside calcium alginate microgels (diameter = 280 µm) using a vibrating nozzle injector. Confocal microscopy indicated that insulin was successfully encapsulated inside the microgels and remained inside them after they were exposed to simulated gastric conditions. Localized fluorescence intensity measurements indicated that the internal pH of the antacid-loaded microgels was around pH 7.4 after incubation in acidic gastric fluids but below the limit of detection (pH < 4) in the antacid-free microgels. After incubation in small intestine conditions, around 30% of the insulin was released from the antacid-loaded microgels over a 2 h period. Encapsulation of insulin within the antacid-loaded microgels increased its biological activity after exposure to simulated gastric conditions. In particular, the encapsulated insulin significantly increased Akt phosphorylation at both Thr308 and Ser473 in L6 myotubes when compared to free insulin.

A comparative study on the raft chemical properties of various alginate antacid raft-forming products.

OBJECTIVE: Research to measure the chemical characterization of alginate rafts for good raft performance and ascertain how formulation can affect chemical parameters. SIGNIFICANCE: A selection of alginate formulations was investigated all claiming to be proficient raft formers with significance between products established and ranked. METHODS: Procedures were selected which demonstrated the chemical characterization allowing rafts to effectively impede the reflux into the esophagus or in severe cases to be refluxed preferentially into the esophagus and exert a demulcent effect, with focus of current research on methods which complement previous studies centered on physical properties. The alginate content was analyzed by a newly developed HPLC method. Methods were used to determine the neutralization profile and the acid neutralization within the raft determined along with how raft structure affects neutralization. RESULTS: Alginate content of Gaviscon Double Action (GDA) within the raft was significantly superior (p < .0001) to all competitor products. The two products with the highest raft acid neutralization capacity were GDA and Rennie Duo, the latter product not being a raft former. Raft structure was key and GDA had the right level of porosity to allow for longer duration of neutralization. CONCLUSION: Alginate formulations require three chemical reactions to take place simultaneously: transformation to alginic acid, sodium carbonate reacting to form carbon dioxide, calcium releasing free calcium ions to bind with alginic acid providing strength to raft formation. GDA was significantly superior (p <.0001) to all other comparators.

Nitrogen-doped graphene quantum dot for direct fluorescence detection of Al3+ in aqueous media and living cells.

Graphene quantum dot (GQD) has been attractive in analytical science field due to its low toxicity, stable photoluminescence. Herein, nitrogen-doped GQD (N-GQD) was prepared by a facile solvothermal treatment of GO using dimethylformamide, and exhibited a green emission with 23.1% quantum yield. The N-GQD probe showed a selective and sensitive fluorescence enhancement response to Al3+, the mechanism might be the formation of a complex between Al3+ and N-GQD constrained the photo-induced electron transfer (PET) process of N-GQD itself. With Benesi-Hildebrand equation, the binding constant and molar ratio between N-GQD and Al3+ was calculated to be 4.6 × 104Lmol-1 and 1:1 respectively. The pKa value of N-GQD was also determined to be 4.4 by capillary electrophoresis. In pH 4.0 PBS solution, there was a good linear relation between the fluorescence intensity and the logarithm of concentration of Al3+ in the range of 2.5-75µmolL-1, the limit of detection (3σ) was 1.3µmolL-1. This "Off - On" fluorescence method had been applied to accurate quantification of aluminum in hydrotalcite tablets. What's more, the fluorescence switch property of N-GQD was explored by alternate addition of Al3+ and EDTA. The probe was also utilized for detection Al3+ in living cells due to its excellent biocompatibility.

Efficacy of alginate-based reflux suppressant and magnesium-aluminium antacid gel for treatment of heartburn in pregnancy: a randomized double-blind controlled trial.

The aim of this study was to compare the therapeutic efficacy of alginate-based reflux suppressant and magnesium-aluminium antacid gel for treatment of heartburn in pregnancy. A double-blinded, randomized, controlled trial was conducted. One hundred pregnant women at less than 36 weeks gestation with heartburn at least twice per week were randomized to either alginate-based reflux suppressant or to magnesium-aluminium antacid gel. Details of heartburn were recorded before beginning the treatment and the second week of study. Primary outcome measure was the improvement of heartburn frequency after treatment and secondary outcome were the improvement of heartburn intensity, quality of life, maternal satisfaction, maternal side effects, pregnancy and neonatal outcomes. There was no difference between treatment and control groups in improvement of heartburn frequency (80% vs 88%, p = 0.275), 50% reduction of frequency of heartburn (56% vs 52%, p = 0.688), improvement of heartburn intensity (92% vs 92%, p = 1.000) and 50% reduction of heartburn intensity (68% vs 80% cases, p = 0.075). There were also no significant differences in quality of life, maternal satisfaction, maternal side effects, pregnancy and neonatal outcomes. Alginate-based reflux suppressant was not different from magnesium-aluminium antacid gel in the treatment of heartburn in pregnancy.

Mechanistic insights into the bleaching of melanin by alkaline hydrogen peroxide.

This work aims to determine the roles of reactive oxygen species HO∙ and HO2- in the bleaching of melanins by alkaline hydrogen peroxide. Experiments using melanosomes isolated from human hair indicated that the HO∙ radical generated in the outside solution does not contribute significantly to bleaching. However, studies using soluble Sepia melanin demonstrated that both HO2- and HO∙ will individually bleach melanin. Additionally, when both oxidants are present, bleaching is increased dramatically in both rate and extent. Careful experimental design enabled the separation of the roles and effects of these key reactive species, HO∙ and HO2-. Rationalisation of the results presented, and review of previous literature, allowed the postulation of a simplified general scheme whereby the strong oxidant HO∙ is able to pre-oxidise melanin units to o-quinones enabling more facile ring opening by the more nucleophilic HO2-. In this manner the efficiency of the roles of both species is maximised.

Effects of ranitidine (antacid), food, and formulation on the pharmacokinetics of fostamatinib: results from five phase I clinical studies.

PURPOSE: Fostamatinib is an orally dosed phosphate prodrug that is cleaved by intestinal alkaline phosphatase to the active metabolite R406. Clinical studies were performed to assess the effect of food and ranitidine on exposure, to support in vitro-in vivo relationships (IVIVR) understanding and formulation transitions and to investigate absolute oral bioavailability. METHODS: A series of in vitro dissolution and clinical pharmacokinetic studies were performed to support the design and introduction of a new formulation, understand the impact of changes in in vitro dissolution on in vivo performance for two fostamatinib formulations, to characterize the effects of food and ranitidine on exposure, and determine the absolute oral bioavailability. RESULTS: The in vivo performance of fostamatinib was generally insensitive to changes in in vitro dissolution performance, although marked slowing of the dissolution rate did impact exposures. Food and ranitidine had minor effects on R406 exposure that were not considered clinically relevant. The absolute oral bioavailability of fostamatinib was 54.6 %. CONCLUSIONS: The absolute oral bioavailability of fostamatinib was ~55 %. Food and ranitidine had minor effects on R406 exposure. An in vitro dissolution versus clinical performance relationship was determined that supported formulation transitions.

Iron Supplements and Magnesium Peroxide: An Example of a Hazardous Combination in Self-Medication.

The use of self-medication, which includes dietary supplements and over-the-counter drugs, is still on the rise, while safety issues are not well addressed yet. This especially holds for combinations. For example, iron supplements and magnesium peroxide both produce adverse effects via the formation of reactive oxygen species (ROS). This prompted us to investigate the effect of the combination of three different iron supplements with magnesium peroxide on ROS formation. Hydroxyl radical formation by the three iron supplements either combined with magnesium peroxide or alone was determined by performing a deoxyribose assay. Free iron content of iron supplements was determined using ferrozine assay. To determine hydrogen peroxide formation by magnesium peroxide, a ferrous thiocyanate assay was performed. Finally, electron spin resonance spectroscopy (ESR) was performed to confirm the formation of hydroxyl radicals. Our results show that magnesium peroxide induces the formation of hydrogen peroxide. All three iron supplements induced the formation of the extremely reactive hydroxyl radical, although the amount of radicals formed by the different supplements differed. It was shown that combining iron supplements with magnesium peroxide increases radical formation. The formation of hydroxyl radicals after the combination was confirmed with ESR. All three iron supplements contained labile iron and induced the formation of hydroxyl radicals. Additionally, magnesium peroxide in water yields hydrogen peroxide, which is converted into hydroxyl radicals by iron. Hence, iron supplements and magnesium peroxide is a hazardous combination and exemplifies that more attention should be given to combinations of products used in self-medication.

Calcium Carbonate.

Calcium carbonate is a chemical compound with the formula CaCO3 formed by three main elements: carbon, oxygen, and calcium. It is a common substance found in rocks in all parts of the world (most notably as limestone), and is the main component of shells of marine organisms, snails, coal balls, pearls, and eggshells. CaCO3 exists in different polymorphs, each with specific stability that depends on a diversity of variables.