scholarly journals Bioelution, Bioavailability, and Toxicity of Cobalt Compounds Correlate

2020 ◽  
Vol 174 (2) ◽  
pp. 311-325 ◽  
Author(s):  
Ruth Danzeisen ◽  
David Lee Williams ◽  
Vanessa Viegas ◽  
Michael Dourson ◽  
Steven Verberckmoes ◽  
...  
Keyword(s):  
Adverse Effect ◽  
Gastric Fluid ◽  
Simulated Gastric Fluid ◽  
In Vivo Toxicity ◽  
Invaluable Tool ◽  
Adverse Effect Level ◽  
In Vitro Bioaccessibility ◽  
The Difference

Abstract Based on the wide use of cobalt substances in a range of important technologies, it has become important to predict the toxicological properties of new or lesser-studied substances as accurately as possible. We studied a group of 6 cobalt substances with inorganic ligands, which were tested for their bioaccessibility (surrogate measure of bioavailability) through in vitro bioelution in simulated gastric and intestinal fluids. Representatives of the group also underwent in vivo blood kinetics and mass balance tests, and both oral acute and repeated dose toxicity (RDT) testing. We were able to show a good correlation between high in vitro bioaccessibility with high in vivo bioavailability and subsequent high in vivo toxicity; consequently, low in vitro bioaccessibility correlated well with low in vivo bioavailability and low in vivo toxicity. In vitro bioelution in simulated gastric fluid was the most precise predictor of the difference in the oral RDT lowest observed adverse effect levels of 2 compounds representing the highly and poorly bioaccessible subset of substances. The 2 compounds cobalt dichloride hexahydrate and tricobalt tetraoxide differed by a factor of 440 in their in vitro bioaccessibility and by a factor of 310 in their RDT lowest observed adverse effect level. In summary, this set of studies shows that solubility, specifically in vitro bioelution in simulated gastric fluid, is a good, yet conservative, predictor of in vivo bioavailability and oral systemic toxicity of inorganic cobalt substances. Bioelution data are therefore an invaluable tool for grouping and read across of cobalt substances for hazard and risk assessment.

scholarly journals Gastrin and Nitric Oxide Production in Cultured Gastric Antral Mucosa Are Altered in Response to a Gastric Digest of a Dietary Supplement

2021 ◽  
Vol 8 ◽  
Author(s):  
Jennifer L. MacNicol ◽  
Wendy Pearson
Keyword(s):  
Nitric Oxide ◽  
Cell Viability ◽  
Dietary Supplement ◽  
Culture Media ◽  
Gastric Fluid ◽  
Simulated Gastric Fluid ◽  
Antral Mucosa ◽  
The Impact

In vitro organ culture can provide insight into isolated mucosal responses to particular environmental stimuli. The objective of the present study was to investigate the impact of a prolonged culturing time as well as the addition of acidic gastric fluid into the in vitro environment of cultured gastric antral tissue to evaluate how altering the commonly used neutral environment impacted tissue. Furthermore, we aimed to investigate the impact of G's Formula, a dietary supplement for horses, on the secretion of gastrin, interleukin1-beta (IL-1β), and nitric oxide (NO). These biomarkers are of interest due to their effects on gastric motility and mucosal activity. Gastric mucosal tissue explants from porcine stomachs were cultured in the presence of a simulated gastric fluid (BL, n = 14), simulated gastric fluid containing the dietary supplement G's Formula (DF, n = 12), or an equal volume of phosphate buffered saline (CO, n = 14). At 48 and 60 h, 10−5 M carbachol was used to stimulate gastrin secretion. Cell viability was assessed at 72 h using calcein and ethidium-homodimer 1 staining. Media was analyzed for gastrin, IL-1β, and NO at 48, 60, and 72 h. There were no effects of treatment or carbachol stimulation on explant cell viability. Carbachol resulted in a significant increase in gastrin concentration in CO and DF treatments, but not in BL. NO was higher in CO than in BL, and NO increased in the CO and DF treatments but not in BL. In conclusion, the addition of carbachol and gastric digests to culture media did not impact cell viability. The use of an acidic gastric digest (BL) reduced the effect of cholinergic stimulation with carbachol at a concentration of 10−5 M and reduced NO secretion. The addition of the dietary supplement to the gastric digest (DF) appeared to mediate these effects within this model. Further research is required to evaluate the specific effects of this dietary supplement on direct markers of mucosal activity and the functional relevance of these results in vivo.

scholarly journals Liposome-Encapsulated Bacteriophages for Enhanced Oral Phage Therapy against Salmonella spp.

2015 ◽  
Vol 81 (14) ◽  
pp. 4841-4849 ◽  
Author(s):  
Joan Colom ◽  
Mary Cano-Sarabia ◽  
Jennifer Otero ◽  
Pilar Cortés ◽  
Daniel Maspoch ◽  
...  
Keyword(s):  
Intestinal Tract ◽  
Positive Charge ◽  
Phage Therapy ◽  
Gastric Fluid ◽  
Simulated Gastric Fluid ◽  
Salmonella Spp ◽  
Content Type ◽  
The Difference ◽  
Over Time

ABSTRACTBacteriophages UAB_Phi20, UAB_Phi78, and UAB_Phi87 were encapsulated in liposomes, and their efficacy in reducingSalmonellain poultry was then studied. The encapsulated phages had a mean diameter of 309 to 326 nm and a positive charge between +31.6 and +35.1 mV (pH 6.1). In simulated gastric fluid (pH 2.8), the titer of nonencapsulated phages decreased by 5.7 to 7.8 log units, whereas encapsulated phages were significantly more stable, with losses of 3.7 to 5.4 log units. The liposome coating also improved the retention of bacteriophages in the chicken intestinal tract. When cocktails of the encapsulated and nonencapsulated phages were administered to broilers, after 72 h the encapsulated phages were detected in 38.1% of the animals, whereas the nonencapsulated phages were present in only 9.5%. The difference was significant. In addition, in anin vitroexperiment, the cecal contents of broilers promoted the release of the phages from the liposomes. In broilers experimentally infected withSalmonella, the daily administration of the two cocktails for 6 days postinfection conferred similar levels of protection againstSalmonellacolonization. However, once treatment was stopped, protection by the nonencapsulated phages disappeared, whereas that provided by the encapsulated phages persisted for at least 1 week, showing the enhanced efficacy of the encapsulated phages in protecting poultry againstSalmonellaover time. The methodology described here allows the liposome encapsulation of phages of different morphologies. The preparations can be stored for at least 3 months at 4°C and could be added to the drinking water and feed of animals.

scholarly journals Crystal products of lamotrigine-citric acid for improvement of in vitro drug release in simulated gastric fluid

2020 ◽  
pp. 49-49
Author(s):  
Bhabani Satapathy ◽  
Asuprita Patel ◽  
Rudra Sahoo ◽  
Subrata Mallick
Keyword(s):  
Citric Acid ◽  
Drug Release ◽  
Crystal Engineering ◽  
Oral Absorption ◽  
Gastric Fluid ◽  
In Vivo Studies ◽  
Simulated Gastric Fluid ◽  
Drug Development Research

Crystal engineering is an integral part of the drug development research. Crystal forms can modify the physicochemical properties of the parent drug molecule. The present work was aimed at the synthesis and characterization of crystalline product of lamotrigine (LT), a FDA approved anti-epileptic drug, with citric acid (CA) to improve its release in gastric region and oral absorption. The crystalline products of LT-CA were developed by solvent evaporation method using ethanol-water as the solvent system. Appearance of new charac-teristic peaks in the FTIR spectra for the crystal products indicated formation of new crystal state. In DSC thermogram, melting point of the experimental crystal products was different than that of the pure drug. Further, formation of new crystalline phase was confirmed from XRD data through the identification of new sharp peaks for the selected crystal products. A higher cumulative percen-tage of drug release was observed for the crystal products than the free drug within 60 min of drug release in simulated gastric fluid. However, in vivo studies are warranted for the future technology transfer of the product at industrial scale.

DEVELOPMENT AND CHARACTERIZATION OF NOVEL SITE SPECIFIC FLOATING-MUCOADHESIVE TABLETS BEARING 5-FLOUROURACIL FOR STOMACH TARGETING.

INDIAN DRUGS ◽  
2014 ◽  
Vol 51 (09) ◽  
pp. 23-30
Author(s):  
P Bhardwaj ◽  
◽  
R Singh ◽  
A Swarup
Keyword(s):  
Drug Release ◽  
Methyl Cellulose ◽  
Gastric Fluid ◽  
Simulated Gastric Fluid ◽  
Wet Granulation ◽  
Prolonged Release ◽  
Mucoadhesive Tablets

Object of present investigation was to develop and characterize such a gastroretentive tablet, which provides the synergism effect of adhesiveness and floating property for prolonged release of 5-flourouracil within the stomach. The floating mucoadhesive tablets were prepared by the wet granulation method using different ratios of hydroxy propyl methyl cellulose (HPMC K4MCR) and Carbopol 934P as polymers. The prepared floating-mucoadhesive tables were characterized for hardness, detachment stress, floating properties, swelling index and surface morphology by SEM. The in vitro drug release and floating behaviour were studied in simulated gastric fluid (SGF) at pH 1.2. Different kinetic models for drug release were as well applied. Formulations of T-9 batch were furthermore subjected to stability and in vivo radiographic studies.

scholarly journals A Liposomal Formulation for Improving Solubility and Oral Bioavailability of Nifedipine

Molecules ◽  
2020 ◽  
Vol 25 (2) ◽  
pp. 338 ◽  
Author(s):  
Ye Bi ◽  
Bingcong Lv ◽  
Lianlian Li ◽  
Robert J. Lee ◽  
Jing Xie ◽  
...  
Keyword(s):  
Oral Bioavailability ◽  
In Vitro Release ◽  
Control Release ◽  
Gastric Fluid ◽  
Oral Route ◽  
Simulated Gastric Fluid ◽  
Scanning Calorimetry ◽  
Time Curve

Proliposomes were used to improve the solubility and oral bioavailability of nifedipine. Nifedipine proliposomes were prepared by methanol injection-spray drying method. The response surface method was used to optimize formulation to enhance the encapsulation efficiency (EE%) of nifedipine. The particle size of nifedipine proliposomes after rehydration was 114 nm. Surface morphology of nifedipine proliposomes was observed by a scanning electron microscope (SEM) and interaction of formulation ingredients was assessed by differential scanning calorimetry (DSC). The solubility of nifedipine is improved 24.8 times after forming proliposomes. In vitro release experiment, nifedipine proliposomes had a control release effect, especially in simulated gastric fluid. In vivo, nifedipine proliposomes significantly improved the bioavailability of nifedipine. The area under the concentration-time curve (AUC0–∞) of nifedipine proliposomes was about 10 times than nifedipine after oral administration. The elimination half-life (T1/2β) of nifedipine was increased from 1.6 h to 6.6 h. In conclusion, proliposomes was a promising system to deliver nifedipine through oral route and warranted further investigation.

scholarly journals Comparative survival of commercial probiotic formulations: tests in biorelevant gastric fluids and real-time measurements using microcalorimetry

2015 ◽  
Vol 6 (1) ◽  
pp. 141-151 ◽  
Author(s):  
M. Fredua-Agyeman ◽  
S. Gaisford
Keyword(s):  
Real Time ◽  
Gastric Fluid ◽  
Simulated Gastric Fluid ◽  
Fed State ◽  
Fasted State ◽  
Nutritional Advice ◽  
Freeze Dried ◽  
Viable Bacteria

The large number of probiotic products now available makes the decision about which product to choose difficult both for the consumer and for the specialist providing dietary/nutritional advice. Data on the viability of the bacteria in these products, in an in vivo situation, are therefore important. This study was designed to explore the comparative health and survival of probiotic species in various commercial formulations, using more realistic test systems. This might allow further understanding of factors that must be controlled to optimise the delivery of live healthy bacteria to the lower gut. A total of eight commercially available probiotic preparations were selected for enumeration tests and in vitro gastric tolerance tests. Tolerance assays were conducted in porcine gastric fluid (PGF) fed and fasted state (pH 3.4±0.04), simulated gastric fluid (SGF, pH adjusted to 1.2 and 3.4) and fasted state simulated gastric fluid (FaSSGF, pH adjusted to 1.6 and 3.4). Isothermal microcalorimetry was also used to measure real-time growth of probiotics after exposure to simulated gastric fluid. Results from the enumeration tests indicated that recovery of viable organisms per dose is the same as or better than the stated label claims for liquid-based formulations, but lower than the stated claim for freeze-dried products. Results from the in vitro tolerance tests overall suggest that the PGF provided a harsher environment than the simulated systems at similar pH. In general, liquid-based products tested tended to give superior results in terms of survival compared with the freeze-dried products tested. Results from tests in the fed state in PGF suggested that food greatly affects viability. Microcalorimetric data showed that for some products probiotic species were able to grow following exposure to gastric fluid, suggesting that viable bacteria reach the gut in vivo.

Application of SRMS 154 as Sustained Release Matrix for the Delivery of Stavudine: In vitro and in vivo Evaluation and Effect of Poloxamer 188 on the Properties of the Tablets

2020 ◽  
Vol 20 (1) ◽  
pp. 76-87
Author(s):  
S.A. Chime ◽  
A.A. Attama ◽  
G.C. Onunkwo
Keyword(s):  
Sustained Release ◽  
Area Under The Curve ◽  
Gastric Fluid ◽  
Simulated Gastric Fluid ◽  
Time Range ◽  
In Vivo Evaluation ◽  
Simulated Intestinal Fluid ◽  
Poloxamer 188

Background: Stavudine is an antiretroviral therapy with so many side effects and has a short half-life of 1.5 h. It degrades to thymine under hydrolytic, oxidative and photolytic conditions hence has major formulation challenges. Objectives: To formulate sustained release lipid based stavudine and to study the properties of the formulations by in vitro and in vivo methods. Methods: Stavudine tablets were formulated by moulding using validated tablets moulds. The carrier used were solidified reverse micellar solution (SRMS) made up of varying ratios of hydrogenated palm oil and Phospholipid admixtures. Evaluation tests were carried out on the tablets using both Pharmacopoeial and non Pharmacopoeial test. Drug release was studied in both simulated gastric fluid (SGF, pH 1.2) and simulated intestinal fluid (SIF, pH 7.2). In vivo release was studied using Wistar rats. Results: The results showed that stavudine tablets exhibited weight range of 372 ± 0.14 to 386 ± 0.52 mg, friability ranged from 0.00 to 0.13 % and hardness ranged from 4.27 ± 0.25 to 5.30 ± 0.21 Kgf. Tablets formulated with SRMS 1:2 had erosion time range of 60.80 ± 1.23 to 87.90 ± 2.33 min and was affected significantly by the presence of Poloxamer 188 (p < 0.05). The formulations exhibited T100 % at 10 to13 h in SIF. Stavudine tablets showed the area under the curve (AUC) of 854.0 μg/h/ml, significantly higher than the AUC of the reference (p < 0.05). Conclusion: Stavudine SRMS-based tablets had good stability and sustained release properties. Formulations containing 1 % Poloxamer 188 exhibited enhanced in vivo absorption and hence could be used once daily in order to enhance the bioavailability of this drug..

scholarly journals Safety assessment of nicotinamide riboside, a form of vitamin B3

2016 ◽  
Vol 35 (11) ◽  
pp. 1149-1160 ◽  
Author(s):  
DB Conze ◽  
J Crespo-Barreto ◽  
CL Kruger
Keyword(s):  
Adverse Effect ◽  
Micronucleus Assay ◽  
Positive Control ◽  
Vitamin B3 ◽  
Nicotinamide Riboside ◽  
Chromosome Aberration Assay ◽  
Adverse Effect Level ◽  
Effect Level

Nicotinamide riboside (NR) is a naturally occurring form of vitamin B3 present in trace amounts in some foods. Like niacin, it has been shown to be a precursor in the biosynthesis of nicotinamide adenine dinucleotide (NAD+). The safety of Niagen™, a synthetic form of NR, was determined using a bacterial reverse mutagenesis assay (Ames), an in vitro chromosome aberration assay, an in vivo micronucleus assay, and acute, 14-day and 90-day rat toxicology studies. NR was not genotoxic. There was no mortality at an oral dose of 5000 mg/kg. Based on the results of a 14-day study, a 90-day study was performed comparing NR at 300, 1000, and 3000 mg/kg/day to an equimolar dose of nicotinamide at 1260 mg/kg/day as a positive control. Results from the study show that NR had a similar toxicity profile to nicotinamide at the highest dose tested. Target organs of toxicity were liver, kidney, ovaries, and testes. The lowest observed adverse effect level for NR was 1000 mg/kg/day, and the no observed adverse effect level was 300 mg/kg/day.

Study on Bioavailability of Sulfadiazine Tablets in Man

1976 ◽  
Vol 10 (7) ◽  
pp. 402-408 ◽  
Author(s):  
W. A. Ritschel ◽  
G. Ritschel ◽  
C. R. Buncher ◽  
J. Rotmensch
Keyword(s):  
Latin Square ◽  
Gastric Fluid ◽  
The Other ◽  
Intestinal Fluid ◽  
Disintegration Time ◽  
Cumulative Urinary Excretion ◽  
Time Periods ◽  
The Difference

Sulfadiazine Tablets USP, 500 mg, from 3 different manufacturers were tested in vitro and in vivo. Dissolution rate and disintegration time were measured in water, artificial gastric fluid, and artificial intestinal fluid. Disintegration and dissolution were fastest in artificial gastric fluid. Product I was superior in disintegration to the other two products, whereas product 2 was superior in dissolution. The in vivo study was designed as a Latin square so that each of the 3 treatments was given to each of the 3 subjects at each of the 3 time periods. Two-way analysis of variance was done using the cumulative urinary excretion of free and total sulfadiazine after 24 and 120 hours. Although the extent of bioavailability of product 1 and 2 was only 78 and 73 percent, respectively, statistically significant differences were found only at 24 hours. Judging from both rate and extent of bioavailability, product 3 was superior to products 1 and 2. The difference between in vitro and in vivo data is noted.

NT4X-167; Novel N-terminal Aβ specific antibody, prevents in vitro and in vivo toxicity of highly toxic Aβ4-42 species

2015 ◽  
Vol 48 (06) ◽  
Author(s):  
G Antonios ◽  
H Borgers ◽  
T Pilot ◽  
V Pena ◽  
T Bayer
Keyword(s):  
Specific Antibody ◽  
In Vivo Toxicity
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