fumaric-acid and tartaric-acid

Orally dosed drugs must dissolve in the gastrointestinal (GI) tract before being absorbed through the epithelial cell membrane.

Topics: Administration, Oral; Betaine; Biological Availability; Chemistry, Pharmaceutical; Computer Simulation; Drug Design; Drug Liberation; Excipients; Fumarates; Gastrointestinal Absorption; Humans; Hydrogen-Ion Concentration; Models, Biological; Solubility; Tartrates

To judge the developability and analyze functional mechanism of co-amorphouses, we investigated the physicochemical properties of co-amorphouses and compare the properties with the co-crystals having the same drug and counters. Co-amorphous compounds are a novel approach to improve the physicochemical properties of drugs. A co-amorphous is in an amorphous solid state allowing non-ionic interactions between drug molecules and counter molecules. The co-amorphous compounds composed of itraconazole (ITZ) with the organic carboxyl acid, fumaric acid (FA) or L-tartaric acid (TA), were prepared by mechanical grinding. Potential interactions within ITZ-FA co-amorphous were assessed by Raman spectroscopy. ITZ-FA co-amorphous was not crystallized as the co-crystal or as a single ITZ crystal, suggesting that the amorphous state, like the amorphous solid dispersion, was physically stable and that ITZ-FA co-amorphous was also chemically stable. In contrast, no clear interactions were observed within ITZ-TA co-amorphous, and the co-amorphous was physically stable but chemically unstable. The solubility of the co-amorphous state was much higher than those of ITZ crystal and the co-crystals and was almost identical to that of amorphous ITZ. A co-amorphous compound like ITZ-FA co-amorphous might be feasible to implement in the development of solid drug products and bring some merits compared to the co-crystals, and the function is governed by the interaction between a drug and a counter. The co-amorphous approach may be an effective strategy for drug development and can contribute to the production of novel drugs with improved functions.

Topics: Catalysis; Chemistry, Physical; Cobalt; Crystallization; Fumarates; Itraconazole; Molecular Structure; Solubility; Tartrates

Cocrystal forming ability of antiviral drug acyclovir (ACV) with different coformers was studied. Three cocrystals containing ACV with fumaric acid, malonic acid, and DL-tartaric acid were isolated. Methods of cocrystallization included grinding with dropwise solvent addition and solvent evaporation. The cocrystals were characterized by powder X-ray diffraction, differential scanning calorimetry, and thermogravimetric analysis. The crystal structure of the cocrystal with fumaric acid as conformer was determined by single crystal X-ray diffraction. Formation of supramolecular synthon was observed in the cocrystal. Stability with respect to relative humidity for the three cocrystals was evaluated. The aqueous solubility of the ACV-cocrystal materials was significantly improved with a maximum of malonic acid cocrystal, which was about six times more soluble at 35°C compared with that of parent ACV. The dissolution profile indicates that at any particular dissolution time, the concentration of cocrystals in the solution was higher than that of the parent ACV, and malonic acid cocrystals had a maximum release of about twice than the hydrated ACV.

Topics: Acyclovir; Antiviral Agents; Calorimetry, Differential Scanning; Chemical Phenomena; Crystallization; Crystallography, X-Ray; Dicarboxylic Acids; Drug Compounding; Drug Stability; Fumarates; Hydrogen Bonding; Kinetics; Malonates; Models, Molecular; Molecular Conformation; Pharmaceutic Aids; Powder Diffraction; Solubility; Tartrates; Thermogravimetry

The characterization of the metabolites accumulated in the grapes of specific cultivars grown in different climates is of particular importance for viticulturists and enologists. In the present study, the metabolite profiling of grapes from the cultivars, Alvarinho, Arinto and Padeiro de Basto, of two Portuguese Controlled Denomination of Origin (DOC) regions (Vinho Verde and Lisboa) was investigated by gas chromatography-coupled time-of-flight mass spectrometry (GC-TOF-MS) and an amino acid analyzer. Primary metabolites, including sugars, organic acids and amino acids, and some secondary metabolites were identified. Tartaric and malic acids and free amino acids accumulated more in grapes from vines of the DOC region of Vinho Verde than DOC Lisboa, but a principal component analysis (PCA) plot showed that besides the DOC region, the grape cultivar also accounted for the variance in the relative abundance of metabolites. Grapes from the cultivar, Alvarinho, were particularly rich in malic acid and tartaric acids in both DOC regions, but sucrose accumulated more in the DOC region of Vinho Verde.

Topics: Amino Acids; Chromatography, Gas; Citric Acid; Fructose; Fruit; Fumarates; Geography; Glucose; Malates; Maleates; Mass Spectrometry; Metabolome; Metabolomics; Portugal; Principal Component Analysis; Species Specificity; Succinic Acid; Sucrose; Tartrates; Vitis

An ion-exclusion chromatographic method for the simultaneous determination of organic acids in rice wine was developed. An IC-Pak Ion Exclusion column (300 mm x 7.8 mm, 7 microm) was used at 50 degrees C. The mobile phases were H2SO4 (phase A) and acetonitrile (phase B) (98:2, v/v) at a flow rate of 0.5 mL/min. The gradient elution program was as follows: 0-40 min, 0.01 mol/L H2SO4 to 0.02 mol/L H2SO4; 40-50 min, 0.01 mol/L H2SO4. The injection volume was 10 microL. The detection wavelength was set at 210 nm. The results showed that oxalic acid, maleic acid, citric acid, tartaric acid, malic acid, ascorbic acid, succinic acid, lactic, fumaric acid, acetic acid, propionic acid, isobutyric acid and butyric acid were completely separated and determined in 30 min. The linear correlation coefficients were above 0.999 7 in the range of 0.001- 1.000 g/L. Under the optimized conditions, the recoveries of organic acids in rice wine were in the range of 93.4% - 103.8% with the relative standard deviations (RSDs, n = 5) of 0.1% - 1.5%. This method is feasible, convenient, fast, accurate and applicable for the quantitative analysis of the organic acids in rice wine.

Topics: Acids; Chromatography, Gel; Fumarates; Malates; Maleates; Oryza; Oxalic Acid; Tartrates; Wine

Sugars, organic acids, and total phenolic content in fruit of 25 wild and cultivated berry species were identified and quantified with high-performance liquid chromatograph. The composition of sugars, organic acids, and total phenolic compounds in various species of Vaccinium, Rubus, Ribes, and Fragaria genus was evaluated. Additonally, total phenolics of less known berry species of the Morus, Amelanchier, Sorbus, Sambucus, Rosa, Lycium, Actinidia, and Aronia genus were determined in wild growing as well as in cultivated fruits. Significant differences in the concentration of sugars and organic acids were detected among the berry species. Glucose and fructose were the most abundant sugars in berry fruits and the major organic acids were malic and citric acid. However, in kiwi fruit, sucrose represented as much as 71.9% of total sugars. Sorbitol has been detected and quantified in chokeberry, rowanberry, and eastern shadbush fruit. The highest content of total analyzed sugars was determined in rowanberry fruit, followed by dog rose, eastern shadbush, hardy kiwifruit, American cranberry, chokeberry, and jostaberry fruit. Rowanberry stands out as the fruit with the highest content of total analyzed organic acids, followed by jostaberry, lingonberry, red gooseberry, hardy kiwifruit, and black currant. The berries of white gooseberry, black currant, red currant, and white currant had the lowest sugar/organic acid ratio and were thus perceptively the sourest species analyzed. On the other hand, the species with highest sugar/organic acid ratio were goji berry, eastern shadbush, black mulberry, and wild grown blackberry. The highest amounts of total phenols were quantified in chokeberry fruit. Wild strawberry, raspberry, and blackberry had 2- to 5-fold more total phenolics compared to cultivated plants.. The fruit of analyzed berry species contained different levels of sugars, organic acids, and total phenolics. Moreover, it has been demonstrated that wild grown species generally contain more phenolics than cultivated ones. This information is interesting for nutritionists as well as berry growers and breeders who can promote the cultivation of species and new cultivars with higher phenolic content.

Topics: Actinidia; Carbohydrates; Chromatography, High Pressure Liquid; Citric Acid; Fragaria; Fruit; Fumarates; Malates; Phenols; Photinia; Plant Extracts; Ribes; Rosaceae; Sambucus; Shikimic Acid; Sorbus; Tartrates; Vaccinium macrocarpon

(1)H NMR spectrometry, FT-IR spectroscopy, as well as molecular modeling at the AM1 level and normal mode analysis were used to characterise the interactions and the formation of inclusion complexes between three organic acids: maleic, fumaric, L-tartaric acids and betaCD. In aqueous medium, the complexation was confirmed by (1)H NMR spectroscopy using two-dimensional technique. The stable geometries of the complexes were determined by molecular modeling. Experimental infrared frequencies were assigned on the base of the vibrational normal mode calculation at the fully optimized geometry for the inclusion complexes. All the results point out the presence of stable inclusion complexes between acids and betaCD at the solid state. These results show the double role of the acid. Correlated with the theoretical and experimental data previously obtained for the miconazole/CD/acids complexes, in function of both acids and CDs structures, the acids can either stabilize the complexes by formation of a multicomponent complex or form acid/CD inclusion complexes, hindering the guest inclusion.

Topics: beta-Cyclodextrins; Dicarboxylic Acids; Fumarates; Hydrogen Bonding; Magnetic Resonance Spectroscopy; Maleates; Miconazole; Models, Molecular; Pharmaceutical Vehicles; Spectroscopy, Fourier Transform Infrared; Tartrates; Thermodynamics

The geometry, frequency and intensity of the vibrational bands of miconazole were derived from the density functional theory (DFT) calculations with the hybrid functional B3LYP and the 6-31G(d) basis set. Starting from the fully AM1 optimized geometries of miconazole/betaCD/acids complexes, the miconazole/acid dimers were reoptimized at the B3LYP/6-31G(d) level. Three acids were studied: maleic, fumaric and l-tartaric acids. To begin with the vibrational spectral data obtained from solid phase in mid FT-IR spectrum of miconazole and its dimers are assigned based on the results of the normal modes calculations. All the observed spectra and the calculated ones are found to be in good agreement. In a second step, theoretical results allowed the assignment of FT-IR spectrum for the miconazole/HPgammaCD inclusion complex produced by supercritical carbon dioxide treatment and confirmed the inclusion of miconazole. The experimental spectra for the miconazole/HPgammaCD/acids complexes prepared by supercritical carbon dioxide processing were also assigned using theoretical results. The results confirmed the presence of a genuine inclusion complex and also the interaction between miconazole and the acid.

Topics: Cyclodextrins; Dimerization; Fumarates; Miconazole; Spectroscopy, Fourier Transform Infrared; Tartrates; Vibration

Due to specific adsorption to variable charge soils, low molecular weight organic acids (LMWOAs) have not been sufficiently extracted, even if common extractants, such as water and 0.1 M sodium hydroxide (NaOH), were employed. In this work, the method for extracting LMWOAs in soils with 0.1 M NaOH was improved for variable charge soils; e.g. 1.0 M potassium fluoride (KF) with pH 4.0 was applied as an extractant jointed with 0.1 M NaOH based on its stronger ability to change the electrochemical properties of variable charge soils by specific adsorption. With the proposed method, the recoveries of oxalic, tartaric, malic, citric and fumaric acids were increased from 83 +/- 4, 93 +/- 1, 22 +/- 2, 63 +/- 5 and 84 +/- 3% to 98 +/- 2, 100 +/- 2, 85 +/- 2, 90 +/- 2 and 89 +/- 2%, respectively, compared with NaOH alone. Simultaneously, the LMWOAs in Agri-Udic Ferrosol with field moisture were measured with a satisfactory result.

Topics: Acids; Citric Acid; Electrochemistry; Fluorides; Fumarates; Hydrogen-Ion Concentration; Lactic Acid; Malates; Molecular Weight; Organic Chemicals; Oxalic Acid; Potassium Compounds; Soil; Soil Pollutants; Tartrates; Time Factors

DcuS is a membrane-associated sensory histidine kinase of Escherichia coli specific for C(4) -dicarboxylates. The nature of the stimulus and its structural prerequisites were determined by measuring the induction of DcuS-dependent dcuB'-'lacZ gene expression. C(4)-dicarboxylates without or with substitutions at C2/C3 by hydrophilic (hydroxy, amino, or thiolate) groups stimulated gene expression in a similar way. When one carboxylate was replaced by sulfonate, methoxy, or nitro groups, only the latter (3-nitropropionate) was active. Thus, the ligand of DcuS has to carry two carboxylate or carboxylate/nitro groups 3.1-3.8 A apart from each other. The effector concentrations for half-maximal induction of dcuB'-'lacZ expression were 2-3 mm for the C(4)-dicarboxylates and 0.5 mm for 3-nitropropionate or d-tartrate. The periplasmic domain of DcuS contains a conserved cluster of positively charged or polar amino acid residues (Arg(107)-X(2)-His(110)-X(9)-Phe(120)-X(26)-Arg(147)-X-Phe(149)) that were essential for fumarate-dependent transcriptional regulation. The presence of fumarate or d-tartrate caused sharpening of peaks or chemical shift changes in HSQC NMR spectra of the isolated C(4)-dicarboylate binding domain. The amino acid residues responding to fumarate or d-tartrate were in the region comprising residues 89-150 and including the supposed binding site. DcuS(R147A) mutant with an inactivated binding site was isolated and reconstituted in liposomes. The protein showed the same (activation-independent) kinase activity as DcuS, but autophosphorylation of DcuS was no longer stimulated by C(4)-dicarboxylates. Therefore, the R147A mutation affected signal perception and transfer to the kinase but not the kinase activity per se.

Topics: Amino Acid Sequence; Binding Sites; Citric Acid; Dicarboxylic Acid Transporters; Dicarboxylic Acids; Enzyme Activation; Escherichia coli; Escherichia coli Proteins; Fumarates; Gene Expression Regulation, Bacterial; Histidine Kinase; Lac Operon; Magnetic Resonance Spectroscopy; Models, Molecular; Molecular Sequence Data; Mutagenesis, Site-Directed; Nitro Compounds; Peptide Fragments; Phosphorylation; Propionates; Protein Kinases; Recombinant Fusion Proteins; Sequence Alignment; Structure-Activity Relationship; Tartrates

It has previously been suggested that organic acids enhance iron absorption. We have studied the effect of nine organic acids on the absorption of Fe(II) and Fe(III) in the human epithelial cell line Caco-2. The effect obtained was dose-dependent, and the greatest increase (43-fold) was observed for tartaric acid (4 mmol/L) on Fe(III) (10 micromol/L). Tartaric, malic, succinic, and fumaric acids enhanced Fe(II) and Fe(III) uptake. Citric and oxalic acid, on the other hand, inhibited Fe(II) uptake but enhanced Fe(III) uptake. Propionic and acetic acid increased the Fe(II) uptake, but had no effect on Fe(III) uptake. Our results show a correlation between absorption pattern and chemical structure; e.g. hydroxyl groups, in addition to carboxyls, were connected with a positive influence. The results may be important for elucidating factors affecting iron bioavailability in the small intestine and for the development of foods with improved iron bioavailability.

Topics: Absorption; Acetic Acid; Caco-2 Cells; Carboxylic Acids; Citric Acid; Ferric Compounds; Ferrous Compounds; Fumarates; Humans; Iron; Malates; Oxalic Acid; Propionates; Succinic Acid; Tartrates

A reliable method for the simultaneous determination of oxalic, fumaric, maleic, and succinic acids in tartaric and malic acids for pharmaceutical use by reversed-phase ion-suppression high performance liquid chromatography is presented. HPLC was achieved on a Nova-Pak C18 column by isocratic elution using water adjusted to pH 2.10-2.15 with perchloric acid, and detection was by UV adsorption at a wavelength of 210 nm. This method was found to be superior to previous liquid chromatography as well as other classical assay, and to be an attractive choice for the analysis of these compounds.

Topics: Chromatography, High Pressure Liquid; Dicarboxylic Acids; Drug Contamination; Evaluation Studies as Topic; Fumarates; Hydrogen-Ion Concentration; Malates; Maleates; Oxalic Acid; Perchlorates; Reproducibility of Results; Succinic Acid; Tartrates

A procedure in which anionic analytes, trapped on ion exchange resin, are simultaneously methylated and released using methyl iodide in either supercritical carbon dioxide or acetonitrile has been extended to polyfunctional organic acids. The combined SFE methylation of fruit juice acids trapped onto ion exchange resin proceeds in good yield producing the methyl esters of fumaric, succinic, malic, tartaric, isocitric and citric acids which are readily separated by GC. Using this procedure low concentrations of one acid can be detected and quantitated in the presence of very high concentrations of another. This new method detects tartaric acid at levels of 10 ppm in juices containing 10,000 ppm citric acid. Quantitation was performed either by using GC-FID with triethyl citrate or diethyl tartrate as internal standards or with the element specific calibration capability of the GC-AED. A simple new technique for the determination of citric/isocitric acid ratio is now available. Also, in contrast to HPLC methods, the identity of an analyte is readily confirmed by GC-MS.

Topics: Beverages; Citric Acid; Fruit; Fumarates; Gas Chromatography-Mass Spectrometry; Hydrogen-Ion Concentration; Isocitrates; Malates; Methylation; Succinic Acid; Tartrates

Twenty subjects recorded perceived sourness of solutions of citric + fumaric and of citric + tartaric acids, at pH 3.5 and titratable acidity (TiA) of 4.0 g/l on a moving chart, while parotid saliva flow was recorded via a sialometer . Sourness intensity and flow were greater when citric was the minor acid than when it was dominant. Subjects varied widely in calculated volume of saliva reservoir, but not flow rate (time to 2/3 reservoir vol.). In tartaric-fumaric acid mixtures varying in pH (3.0-3.75) at a constant TiA of 4.0 g/l, and varying in TiA (3.7-4.6 g/l) at a constant pH of 3.5, sourness intensity and parotid flow increased with acidity and decreased with pH. However, eight subjects with a high flow (HF = 1.2 +/- 0.28 g/2 min) and nine subjects with a low flow (LF = 0.43 +/- 0.11 g/2 min) differed widely: (a) In response to variation in stimulus pH and TiA, HF demonstrated marked alteration in flow, but little change in sourness ; LF responded at a lower absolute level, but showed marked changes in sourness and little change in flow; (b) Salivary pH was higher and Na+ was three times greater for the HF than for the LF subjects; and (c) Salivary Ca++ showed a direct relationship with flow and pH among the HF, but an inverse relationship for the LF subjects.

Topics: Adult; Calcium; Citrates; Citric Acid; Female; Fumarates; Humans; Hydrogen-Ion Concentration; Male; Potassium; Saliva; Salivation; Sodium; Tartrates; Taste

Topics: Fumarates; Maleates; Oxalates; Oxalic Acid; Tartrates