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The effect of excipients on the stability of levothyroxine sodium pentahydrate tablets.

Levothyroxine tablets, 50 microg, have been marketed for many decades but have had numerous recalls due to degradation and failure to meet potency. These experiments were devised to study the effects of various excipients on the stability of levothyroxine sodium pentahydrate in aqueous slurries and in formulated tablets. The active alone was found to be stable in the solid state for 6 months at 40 degrees C/75% RH whether stored in open or closed containers, and was found to be non-hygroscopic under normal processing conditions (>30% RH). In aqueous slurries with an excipient, the stability of the active improved as the pH of the slurry was increased from pH 3 to 11. Tablets manufactured with lactose anhydrous, starch, or microcrystalline cellulose failed to meet USP assay requirements at 3 months at 40 degrees C/75% RH. Tablets manufactured with dibasic calcium phosphate or mannitol met USP assay requirements at 3, but not 6 months when stored at 40 degrees C/75% RH. Tablets manufactured with dibasic calcium phosphate and a basic pH modifier, such as sodium carbonate, sodium bicarbonate, or magnesium oxide, met the USP assay requirements at both 3 and 6 months. Thus, the use of basic pH modifiers is a potential technique for improving the stability of levothyroxine sodium pentahydrate tablets.

Adsorption↗

Legislative and environmental issues on the use of ash from coal and municipal sewage sludge co-firing as construction material.

For the economy of any co-firing process, it is important that the common waste management options of ash remain practical. Ash from bituminous coal combustion is typically handed to the construction industry. This paper describes the current European legislation on use of ash for construction purposes. Also, it presents an experimental study on the suitability of fly ash from combustion of mixtures of bituminous coal and municipal sewage sludge as additive to cement and concrete, and for use in open-air construction works, based on the ash chemical composition and the characteristics of the extract of the ash. Presently, two European standards forbid the use of ash from co-firing as additive to cement or concrete. This study shows that ash derived from coal and sewage sludge co-firing contains generally less unburned carbon, alkali, magnesium oxide, chlorine, and sulfate than coal ash. Only the concentration of free lime in mixed ash is higher than in coal, even though, at least up to 25% of the thermal input, still below the requirements of the standards. This ash also meets the requirements for the use of fly ash in open-air construction works--concentration and mobility of few elements--although this management option is forbidden to ash from co-firing. The leaching of Cd, Cr, Cu, Ni, Pb and Zn was investigated with three leaching tests. The concentration of these metals in the extracts was below the detection limit in most cases. The concentration of Cu and Zn in the extract from fly ash was found to increase with increasing share of sewage sludge in the fuel mixture. However, the concentration of these two metals in the extract is not regulated. This study indicates that excluding a priori the use of ash from co-firing as a suitable additive for construction material could cause an unnecessary burden on the environment, since probably ash would have to be disposed of in landfill. However, allowing this requires the modification of current European standards to include limitations on all elements and compounds, absent in coal but which might be present in other fuels, that are deleterious for the quality of construction materials.

Air Pollution↗

Benzylation of aromatic compounds with different crystallites of MgO.

Magnesium oxide nanocrystals are shown to be selective catalysts for the benzylation of aromatics with benzyl chloride, in the order xylene > toluene >> benzene. Normal polycrystalline MgO is not as effective as the nanomaterials. However, at the highest surface area, normally most reactive MgO samples (aerogel prepared AP-MgO) were poorer catalysts than a hexagonal platelet form (CP-MgO) of lower surface area. During the catalysis, the MgO is partially converted to MgCl(2), but crystal shape differences are not washed out. Rate data, differential thermal analysis, and consideration of crystal shapes and faces suggest that the CP-MgO form is most catalytically active because of optimal adsorption, molecular trafficking, and desorption energies. The AP-MgO apparently adsorbs the reactants too strongly, and thereby this hinders the catalytic process. These results serve as another example of where nanocrystalline shape plays an important role.

Journal Article↗

Diversity synthesis via C-H bond functionalization: concept-guided development of new C-arylation methods for imidazoles.

Herein, we have formulated the concept of systematic derivatization of a structural motif via C-H bond functionalization. This concept may not only serve as a blueprint for new strategies in diversity synthesis but also provide systematic guidance for the identification of unsolved and important synthetic challenges. To illustrate this point, 2-phenylimidazole was selected as the core motif for this study, a choice inspired by numerous azole-based synthetics, including pharmaceuticals (compound SB 202190), and also fluorescent and chemiluminescent probes. We were able to show that systematic and comprehensive arylation of the 2-phenylimidazole core was feasible, and in the context of this study new arylation methods were developed. The direct 4-arylation of free 2-phenylimidazole was achieved with iodoarenes as the aryl donors in the presence of palladium catalyst (Pd/Ph(3)P) and magnesium oxide as the base. A complete switch from C-4 to C-2' arylation was accomplished using a ruthenium catalyst [CpRu(Ph(3)P)(2)Cl] and Cs(2)CO(3). The corresponding transformations for (N,2)-diphenylimidazole (C-5 and C-2' arylation) were accomplished via the palladium-based method [Pd(OAc)(2)/Ph(3)P/Cs(2)CO(3)] and a rhodium-catalyzed procedure [Rh(acac)(CO)(2)/Cs(2)CO(3)], respectively. All of the arylation methods described herein demonstrated broad synthetic scope, high efficiency, and exclusive selectivity. Furthermore, these new methods proved to be orthogonal to one another and applicable to sequential arylation schemes. With these methods in hand, arrays of arylated imidazoles may now be accessed in a direct manner from 2-phenylimidazole. This strategy stands in sharp contrast to a traditional approach, wherein a distinct and multistep synthesis would be required for each analogue.

Benzene Derivatives↗

Growth mechanism of textured MgO thin films via SSCVD.

Magnesium oxide thin films have been deposited with use of single source chemical vapor deposition (SSCVD). The resultant films were examined by using transmission electron microscopy, X-ray texture analysis, and pole figure analysis. Due to the nature of the chemical reactions occurring at the surface during SSCVD growth, which result in a high growth rate/low flux environment, films of (111) orientation have been achieved without an amorphous underlayer, an unusual result for films of this orientation. Moreover the films have a strong degree of biaxial texturing in the x-y plane as found with X-ray texture analysis. These findings have important implications for buffer layers in perovskite thin film devices. The mechanism producing these structures has been revealed by using TEM and is discussed here.

Journal Article↗

Atomic scale modelling of the cores of dislocations in complex materials part 2: applications.

In an accompanying article, we have described a methodology for the simulation of dislocations in structurally complex materials. We illustrate the applicability of this method through studies of screw dislocations in a structurally simple ionic ceramic (MgO), a molecular ionic mineral (forsterite, Mg2SiO4), a semi-ionic zeolite (siliceous zeolite A) and a covalent molecular crystalline material (the pharmaceutical, orthorhombic paracetamol-II). We focus on the extent of relaxation and the structure of the dislocation cores and comment on similarities and points of disparity between these materials. It is found that the magnitude of the relaxation varies from material to material and does not simply correlate with the magnitude of the principal elastic constants in an easily predictable fashion, or with the size of the cohesive lattice energy or length of the Burgers vector, which emphasises the need to model the non-linear forces and atomic structure of the core.

Acetaminophen↗

The prevalence of constipation in institutionalized people with intellectual disability.

Constipation is a common problem in people with intellectual disability (ID). Laxatives are frequently prescribed with disappointing results. The prevalence of constipation was investigated in a random population of 215 people with ID (IQ < 50) and constipation was correlated with clinical symptoms. All subjects were scored for bowel habits. Constipation was defined as having a bowel movement less than three times a week or the necessity of using laxatives more than three times a week. Further possible accompanying factors were evaluated. The control subjects were defined as individuals who did not use laxatives. Subjects with constipation were defined as patients and were compared to subjects without constipation (controls). One hundred and forty-nine out of 215 cases (69.3%) showed constipation. Constipation was significantly correlated with non-ambulancy, cerebral palsy, the use of anticonvulsive medication or benzodiazepines, H2-receptor antagonists or proton pump inhibitors, food refusal, and an IQ < 35. Fifty-eight per cent of the patients used bisacodyl or magnesium oxide, 39% lactulose, 13% sodiumlaurylsulphoacetate/sodium citrate/sorbitol and only 10% were given sodium phosphate enemas. Faecal soiling was found in 15% of subjects, while manual evacuation of faeces was performed in nearly 7% of cases. Constipation was randomly demonstrated in almost 70% of the population with ID. Subjects with the above-mentioned accompanying factors are especially at risk for constipation. Contrary to the general population, constipation in people with ID is associated with little use of phosphate enemas, microlax, a low incidence of faecal soiling and manual evacuation of faeces, suggesting an aetiology without distal faecal impaction. The regimen and effect of therapy has to be studied to define adequate treatment schedules.

Adolescent↗

Linear scaling computation of the Fock matrix. VIII. Periodic boundaries for exact exchange at the Gamma point.

A translationally invariant formulation of the Hartree-Fock (HF) Gamma-point approximation is presented. This formulation is achieved through introduction of the minimum image convention (MIC) at the level of primitive two-electron integrals, and implemented in a periodic version of the ONX algorithm [E. Schwegler, M. Challacombe, and M. Head-Gordon, J. Chem. Phys. 106, 9708 (1997)] for linear scaling computation of the exchange matrix. Convergence of the HF-MIC Gamma-point model to the HF k-space limit is demonstrated for fully periodic magnesium oxide, ice, and diamond. Computation of the diamond lattice constant using the HF-MIC model together with the hybrid PBE0 density functional [C. Adamo, M. Cossi, and V. Barone, THEOCHEM 493, 145 (1999)] yields a0=3.569 A with the 6-21G* basis set and a 3x3x3 supercell. Linear scaling computation of the HF-MIC exchange matrix is demonstrated for diamond and ice in the condensed phase.

Journal Article↗

Effect of magnesium salts on the sulphation capacity of limestone slurry.

The effect of different magnesium salts such as MgO, MgSO(4).7H2O and Mg(OH)2 on the total sulphation capacities of limestone slurries prepared from five different limestone samples was investigated. Sulphation reactions of slurries were conducted at a constant temperature of 323 K in a gaseous mixture consisting of 5% O2, 10% CO2, 0.5% SO2 and a balance of nitrogene by volume. It was found that the total sulphation capacities of limestone slurries increased with the addition of MgO and Mg(OH)2 salts and decreased with the addition of MgSO4.7H2O salt. Depending on the chemical composition of the limestone samples the total sulphation capacities of limestone slurries were increased between 22.30% and 75.00% by MgO addition and between 23.70% and 69.00% by Mg(OH)2 addition.

Calcium Carbonate↗

How much light from rectangular scintillation counters?

Theoretical calculations have been made of the efficiency and uniformity of light collection at one end of a large rectangular liquid scintillation counter (80x20x18 cm). Three different arrangements were considered; (1) a system in which all surfaces of the counter other than the collecting surface were transparent to permit total internal reflection, (2) a similar system with a mirror placed close to the end opposite the collecting surface and (3) a system in which external reflectors were placed close to surfaces other than the collecting surface. In all cases, the effects of attenuation of light in the counter medium, inefficient total internal reflection and the reflectivities of external reflectors were considered and illustrated for selected values of these parameters. In an experimental counter of the same dimensions, the amplitude of the spectrum of a collimated 42-K source was used to measure the relative efficiencies of light collection for various reflector arrangements. In general the experimental values agreed with theory and the non-uniformity of response was within the predicted range. It is estimated that about 30% of scintillation light can be collected at one end of such a counter, with a non-uniformity not greater than 10%, if magnesium oxide is used as the external reflector at all other surfaces.

Light↗

Simulations of Kikuchi patterns due to thermal diffuse scattering on MgO crystals.

Inelastic scattering of fast transmission electrons from a perfect crystal is investigated using the Bloch wave theory. A comprehensive expression for the scattering of electrons is given, which includes both elastic and inelastic multiple scatterings. This expression is an extended form of Fujimoto's expression for elastic scattering (J. Phys. Soc. Japan 14:1558 (1959)). For the approximation of single inelastic scattering, the expression becomes equivalent to the formula of Rez et al. (Phil. Mag. 35: 81 (1977)). When thermal diffuse scattering (TDS) is considered using the Einstein model or the scattering factor for TDS given by Hall and Hirsch (Proc. R. Soc. A 286: 158 (1965)), Rossouw and Bursill's expression (Acta Cryst. A 41: 320 (1985)) is derived. This expression has been used in computer simulations of TDS intensity distribution (Kikuchi pattern). It is shown that the simulations for magnesium oxide (MgO) using 357 beams agree quite well with the experimental ones.

Journal Article↗

Review article: practical management of the short bowel.

A shortened small intestine may end at a stoma or be anastomosed to the colon. Patients with a jejunostomy, but not those with a colon, lose large amounts of sodium. The intake and absorption of sodium can be increased by sipping a sodium-glucose solution; stomal loss can be reduced by restricting water or low-sodium drinks. If a stoma is situated less than 100 cm along the jejunum, a constant negative sodium balance may necessitate parenteral saline supplements. Gastric anti-secretory drugs or a somatostatin analogue reduce jejunostomy losses in such patients but do not restore a positive sodium balance. Loperamide or codeine phosphate benefit some patients. Magnesium deficiency can usually be corrected by oral magnesium oxide supplements. An elemental or hydrolysed diet is not beneficial. Patients with a jejunostomy can maintain a normal diet without fat reduction. When the colon is present, unabsorbed carbohydrate is fermented to absorbable short chain fatty acids. Unabsorbed long chain fatty acids and bile salts cause watery diarrhoea and increased colonic oxalate absorption with hyperoxaluria. Such patients benefit from a high carbohydrate, low-fat and low-oxalate diet. Parenteral nutrition is needed only by the few patients unable to maintain health or avoid socially disabling diarrhoea despite these measures.

Diarrhea↗

Immunologic dysfunction among PBB-exposed Michigan dairy farmers.

In 1973 inadvertent contamination occurred in a special farm feed supplement for lactating cows. Polybrominated biphenyls (PBBs) were used in place of magnesium oxide resulting in serious harm to farm animals, including cattle, chickens, geese, ducks. Farm families, accustomed to eating their own products, were most heavily exposed. To further study the impact of PBBs, 45 adult Michigan farm residents who were originally examined in a clinical field survey were further studied with respect to their immunologic status. For comparison, 46 dairy farm residents in Wisconsin, who had not eaten PBB-contaminated food, were examined, as were 79 healthy subjects in New York City. Abnormalities in the Michigan group included significant decrease in absolute numbers and percentages of T and B-lymphocytes and increased number of lymphocytes with no detectable surface markers ("null cells"). Significant reduction of in vitro immune function was noted in 35--40% of the Michigan farm residents who had eaten food containing PBB. Despite the absence of any apparent numerical reduction, both T and B lymphocyte subpopulations of peripheral blood lymphocytes showed evidence of functional defect. Ten of the 45 Michigan farmers studied showed impaired PHA-induced blastogeneic response, due to the decreased number and percent of T-cells in the PBLs. The decreased immune function detected among the PBB-exposed farm residents tended to affect families as a unit and was independent of exposed individuals' age or sex, speaking against the possibility of genetic predisposition.

Accidents↗

In-vitro interaction of a novel immunosuppressant, FK 506, and antacids.

The effect of selected antacids on the amount of FK 506 in solution in simulated gastric juice has been studied. FK 506 (2.5 mg) was incubated in 100 mL simulated gastric fluid (SGF) with the equivalent of 500 mg of various antacids. The addition of Mylanta and Tums resulted in 14 and 30% loss of FK 506, respectively, in 24 h; 98% loss was observed in 12 h in the presence of Mag-Ox; 100% loss was observed in the presence of magnesium oxide powder in 2 h. The loss of FK 506 from these solutions appears to be due to a pH mediated degradation of FK 506. The addition of aluminium hydroxide gel USP (Roxane) to the FK 506 solution resulted in a 35% loss within 2 min but no further loss was noted for 24 h, indicative of adsorption of FK 506. These results suggest that until additional in-vivo studies are carried out, it is prudent not to dose FK 506 and antacids at the same time to avoid potential interactions.

Antacids↗

Adsorption of paracetamol and chloroquine phosphate by some antacids.

The adsorption of paracetamol and chloroquine phosphate onto some antacids with adsorptive properties, has been studied. Dissolution of the drugs from commercial tablets was significantly retarded in the presence of the antacids. The adsorption and retardation of dissolution of both drugs by the adsorbent antacids studied followed the rank order magnesium trisilicate greater than magnesium oxide greater than aluminium hydroxide greater than edible clay. The concomitant administration of the drugs and antacid formulations containing any of these should be discouraged.

Acetaminophen↗