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AAPS PharmSciTech Jul 2022Magnesium stearate (MgSt) is perhaps one of the most frequently used lubricants in tablet formulation due to its superior lubrication capacity, yet it could also...
Magnesium stearate (MgSt) is perhaps one of the most frequently used lubricants in tablet formulation due to its superior lubrication capacity, yet it could also negatively affect the critical quality attributes of pharmaceutical products. Therefore, we provided a rather comprehensive evaluation of another two FDA-approved metallic stearates, sodium stearate (NaSt) and calcium stearate (CaSt), as alternative tablet lubricants. The primary objective of the present study is to comparatively evaluate the physicochemical properties and lubrication efficiency of the three metallic stearates. In addition, it was also aimed to specify the most influential factor for ranking and differentiating the lubricity of various lubricants using principal component analysis. Unit ejection force could be used herein as a simple and the most powerful parameter to evaluate the lubrication performance instead of the friction coefficient. The results suggested that CaSt, MgSt, and NaSt had similar impacts on the mechanical strength of tablets. However, CaSt exhibited insufficient lubrication effects as the formulations containing CaSt showed low pressure transmission ratios, high unit ejection forces, and high friction coefficients. In contrast, both MgSt and NaSt displayed satisfactory lubrication efficiency without negatively impacting tabletability. Notably, the lubrication performance of the formulation containing 0.5 wt% NaSt was almost identical to that of the formulation with 1 wt% MgSt, indicating that NaSt had a remarkable lubrication capability probably due to its high specific surface area. In summary, the findings of this investigation should provide practical information and feasible methodologies to readily determine the lubricity and to sensibly select alternative lubricants for pharmaceutical tablet formulations.
Topics: Lubricants; Lubrication; Stearates; Stearic Acids; Tablets
PubMed: 35882653
DOI: 10.1208/s12249-022-02338-1 -
The EMBO Journal Jan 2023Reprogramming of lipid metabolism is emerging as a hallmark of cancer, yet involvement of specific fatty acids (FA) species and related enzymes in tumorigenesis remains...
Reprogramming of lipid metabolism is emerging as a hallmark of cancer, yet involvement of specific fatty acids (FA) species and related enzymes in tumorigenesis remains unclear. While previous studies have focused on involvement of long-chain fatty acids (LCFAs) including palmitate in cancer, little attention has been paid to the role of very long-chain fatty acids (VLCFAs). Here, we show that depletion of acetyl-CoA carboxylase (ACC1), a critical enzyme involved in the biosynthesis of fatty acids, inhibits both de novo synthesis and elongation of VLCFAs in human cancer cells. ACC1 depletion markedly reduces cellular VLCFA but only marginally influences LCFA levels, including palmitate that can be nutritionally available. Therefore, tumor growth is specifically susceptible to regulation of VLCFAs. We further demonstrate that VLCFA deficiency results in a significant decrease in ceramides as well as downstream glucosylceramides and sphingomyelins, which impairs mitochondrial morphology and renders cancer cells sensitive to oxidative stress and cell death. Taken together, our study highlights that VLCFAs are selectively required for cancer cell survival and reveals a potential strategy to suppress tumor growth.
Topics: Humans; Stearates; Fatty Acids; Mitochondria; Palmitates; Neoplasms
PubMed: 36408830
DOI: 10.15252/embj.2022111268 -
Nutrition Reviews Jul 1955
Topics: Food; Humans; Polyethylene Glycols; Stearates; Stearic Acids
PubMed: 14394517
DOI: 10.1111/j.1753-4887.1955.tb03492.x -
Current Opinion in Chemical Biology Oct 2022Raman microscopy has been used to deduce information about the distributions of endogenous biomolecules without exogenous labeling. Several functional groups, such as... (Review)
Review
Raman microscopy has been used to deduce information about the distributions of endogenous biomolecules without exogenous labeling. Several functional groups, such as alkynes (CC), nitriles (CN), and carbon-deuterium (C-D) bonds, have been employed in recent years as Raman tags to detect target molecules in cells. In this article, we review some recent advances in applications using deuterated fatty acids for lipid analysis, such as investigation of tumor-selective cytotoxicity of γ-linolenic acid (GLA), simultaneous two-color imaging of stearate and oleate using deuterated and protonated alkynes, Raman hyperspectral imaging, and analyses of the physical properties of lipids through spectral unmixing of the C-D vibrational frequencies. In addition, we review some advanced methods for observing intracellular metabolic activities, such as de novo lipogenesis from deuterium-labeled precursors.
Topics: Alkynes; Carbon; Deuterium; Fatty Acids; Nitriles; Oleic Acid; Spectrum Analysis, Raman; Stearates; gamma-Linolenic Acid
PubMed: 35792373
DOI: 10.1016/j.cbpa.2022.102181 -
Molecular Pharmaceutics Oct 2016Excipient-induced salt disproportionation (conversion from salt form to free form) in the solid state during storage or manufacturing is a severe formulation issue that...
Excipient-induced salt disproportionation (conversion from salt form to free form) in the solid state during storage or manufacturing is a severe formulation issue that can negatively influence product performance. However, the role of excipient properties on salt disproportionation and mechanisms of proton transfer between salt and excipients are still unclear. Moreover, knowledge about the formation of disproportionation products and the consequent impact of these reactions products on the disproportionation process is still inadequate. In the present study, three commonly used lubricants (sodium stearate, calcium stearate, and magnesium stearate) were mixed with a hydrochloride salt as binary mixtures to examine their different capabilities for inducing salt disproportionation at a stressed storage condition (40 °C/65% RH). The overall objective of this research is to explore factors influencing the kinetics and extent of disproportionation including surface area, alkalinity, hygroscopicity, formation of new species, etc. In addition, we also aim to clarify the reaction mechanism and proton transfer between the model salt and stearates to provide insight into the in situ formed reaction products. We found that the properties of stearates significantly affect the disproportionation process in the initial stage of storage, while properties of the reaction products negatively affect the hygroscopicity of the powder mixture promoting disproportionation during longer-term storage. In addition, lubrication difference among three stearates was evaluated by performing compaction studies. The findings of this study provide an improved understanding of the proton transfer mechanism between the ionized form of an active pharmaceutical ingredient and excipients in solid dosage forms. It also provides pragmatic information for formulation scientists to select appropriate lubricants and other excipients, and to design robust formulations.
Topics: Drug Compounding; Drug Stability; Excipients; Salts; Solubility; Stearates; Stearic Acids
PubMed: 27542728
DOI: 10.1021/acs.molpharmaceut.6b00630 -
Gut Jun 2021Data from clinical research suggest that certain probiotic bacterial strains have the potential to modulate colonic inflammation. Nonetheless, these data differ between...
OBJECTIVE
Data from clinical research suggest that certain probiotic bacterial strains have the potential to modulate colonic inflammation. Nonetheless, these data differ between studies due to the probiotic bacterial strains used and the poor knowledge of their mechanisms of action.
DESIGN
By mass-spectrometry, we identified and quantified free long chain fatty acids (LCFAs) in probiotics and assessed the effect of one of them in mouse colitis.
RESULTS
Among all the LCFAs quantified by mass spectrometry in Nissle 1917 (EcN), a probiotic used for the treatment of multiple intestinal disorders, the concentration of 3-hydroxyoctadecaenoic acid (C18-3OH) was increased in EcN compared with other strains tested. Oral administration of C18-3OH decreased colitis induced by dextran sulfate sodium in mice. To determine whether other bacteria composing the microbiota are able to produce C18-3OH, we targeted the gut microbiota of mice with prebiotic fructooligosaccharides (FOS). The anti-inflammatory properties of FOS were associated with an increase in colonic C18-3OH concentration. Microbiota analyses revealed that the concentration of C18-3OH was correlated with an increase in the abundance in , and . In culture, produced high concentration of C18-3OH. Finally, using TR-FRET binding assay and gene expression analysis, we demonstrated that the C18-3OH is an agonist of peroxisome proliferator activated receptor gamma.
CONCLUSION
The production of C18-3OH by bacteria could be one of the mechanisms implicated in the anti-inflammatory properties of probiotics. The production of LCFA-3OH by bacteria could be implicated in the microbiota/host interactions.
Topics: Animals; Bacteroidetes; Caco-2 Cells; Cell Membrane Permeability; Chemokine CXCL1; Colitis; Dextran Sulfate; Epithelial Cells; Escherichia coli; Firmicutes; Gastrointestinal Microbiome; Gene Expression; Humans; Interleukin-1beta; Intestinal Mucosa; Mass Spectrometry; Mice; Oligosaccharides; PPAR gamma; Pancreatitis-Associated Proteins; Permeability; Peyer's Patches; Prebiotics; Probiotics; Stearates; Zonula Occludens-1 Protein
PubMed: 32978245
DOI: 10.1136/gutjnl-2020-321173 -
International Journal of Toxicology Dec 2023The Expert Panel for Cosmetic Ingredient Safety reviewed newly available studies since their original assessment in 1982, along with updated information regarding...
The Expert Panel for Cosmetic Ingredient Safety reviewed newly available studies since their original assessment in 1982, along with updated information regarding product types and concentrations of use, and confirmed that Glycol Stearate and Glycol Stearate SE are safe as cosmetic ingredients in the practices of use and concentration as described in this report.
Topics: Toxicity Tests; Stearates; Consumer Product Safety; Surface-Active Agents; Cosmetics; Glycols
PubMed: 37769693
DOI: 10.1177/10915818231204266 -
Archives of Environmental Health Apr 1963
Topics: Carcinogens; Humans; Polyethylene Glycols; Stearates; Stearic Acids; Urinary Bladder; Urinary Bladder Neoplasms
PubMed: 13955486
DOI: 10.1080/00039896.1963.10663431 -
Journal of Controlled Release :... Sep 2005The EPR spectra of the positional isomers n-doxyl stearic acids (n-DSA), with n=5, 12 and 16, and 5-doxyl methyl stearate (5-DMS) structured in the lipid domain of...
The EPR spectra of the positional isomers n-doxyl stearic acids (n-DSA), with n=5, 12 and 16, and 5-doxyl methyl stearate (5-DMS) structured in the lipid domain of intact stratum corneum (SC), are characterized by the thermodynamic equilibrium of two distinct spectral components provided by two different motional states of the spin-labeled chains. A two-component model used in the EPR spectra simulations provided the relative populations of the components, allowing for the calculation of the thermodynamic profile. Based on a detailed investigation, the more motionally restricted population of spin labels (component 1) is found to arise when the spin label is hydrogen-bonded to the polar surfaces of the membranes, while the less motionally restricted population (component 2) is generated by spin labels nonhydrogen-bonded and more deeply inserted in the hydrophobic core. The 5-DSA is bound tightly to the polar surfaces (DeltaG(o)2 --> 1=-1.75 kcal/mol and DeltaH(o)2 --> 1=-13.8 kcal/mol), whereas the more lipophilic 5-DMS has a major spin population stabilized in the hydrophobic core (DeltaG(o)2 --> 10.57 kcal/mol and DeltaH(o)2 --> 1=-9.1 kcal/mol). Upon lipid-depleting SC increases the interactions of the probe with the polar surfaces, thereby decreasing its rotational diffusion. In contrast, the treatment of SC with oleic acid, a permeation enhancer, drastically increases the mobility of the spin labels, particularly that of component 1, and the thermodynamic equilibrium shifts towards the formation of component 2. A mechanism for water permeation in SC is also proposed.
Topics: Animals; Electron Spin Resonance Spectroscopy; Epidermis; Lipid Bilayers; Oleic Acid; Rats; Rats, Wistar; Stearates; Thermodynamics
PubMed: 16006000
DOI: 10.1016/j.jconrel.2005.05.009 -
Scientific Reports Nov 2022Appendicoliths are commonly found obstructing the lumen of the appendix at the time of appendectomy. To identify factors that might contribute to their formation we...
Appendicoliths are commonly found obstructing the lumen of the appendix at the time of appendectomy. To identify factors that might contribute to their formation we investigated the composition of appendicoliths using laser ablation inductively coupled plasma mass spectroscopy, gas chromatography, polarized light microscopy, X-ray crystallography and protein mass spectroscopy. Forty-eight elements, 32 fatty acids and 109 human proteins were identified within the appendicoliths. The most common elements found in appendicoliths are calcium and phosphorus, 11.0 ± 6.0 and 8.2 ± 4.2% weight, respectively. Palmitic acid (29.7%) and stearate (21.3%) are the most common fatty acids. Some stearate is found in crystalline form-identifiable by polarized light microscopy and confirmable by X-ray crystallography. Appendicoliths have an increased ratio of omega-6 to omega-3 fatty acids (ratio 22:1). Analysis of 16 proteins common to the appendicoliths analyzed showed antioxidant activity and neutrophil functions (e.g. activation and degranulation) to be the most highly enriched pathways. Considered together, these preliminary findings suggest oxidative stress may have a role in appendicolith formation. Further research is needed to determine how dietary factors such as omega-6 fatty acids and food additives, redox-active metals and the intestinal microbiome interact with genetic factors to predispose to appendicolith formation.
Topics: Humans; Fatty Acids; Stearates; Appendix; Appendectomy; Chromatography, Gas
PubMed: 36396724
DOI: 10.1038/s41598-022-21397-9