bluuebunny/crossref_metadata_2025 huggingface dataset:
Energy utilization in a fluid energy mill
Authors: Ridgway K , Walton C A
Published: April 2011

A “Gem” fluid energy mill was built into an assembly which allowed the temperature, pressure and quantity of air flowing through it to be measured. The feed rate of powder to be ground was also controlled. The increase in surface area of sodium chloride was determined as a function of air pressure and feed rate in order to establish the conditions for optimum performance.
The mixing of powders flowing down an inclined plane
Authors: Ridgway K , Rupp R , Sanchez A
Published: April 2011

An apparatus has been constructed in which a pair of hoppers feed powders at controlled rates to the top end of a chute in two moving layers, one on top of the other. The layers move down the chute and at the lower end are separated again by an adjustable knife edge. Subsequent analysis of the fractions obtained enables the amount of mixing which has occurred to be determined. Since the mixing takes place under controlled conditions through a known area of contact between the powders, the apparatus measures “powder miscibility”. Two photoelectric cells enabled the powder velocity to be measured. Powder velocities and bed structure are reported for the flow of single layers of sand of various thicknesses. Mixing results are presented, in terms of an effective diffusion coefficient, for the flow of 30/36 mesh sand.
Dissolution rate measurement by an automated dialysis method
Authors: Barzilay R B , Hersey J A
Published: April 2011

An automated dialysis method for measuring the dissolution profiles of unit dose forms is described. The suitability of the method for the evaluation of these profiles has been demonstrated by an examination of tablets of sulphathiazole prepared under different conditions of pressure and excipient content. The addition of the water soluble resin, polyethylene oxide, has been shown to cause a small increase in the dissolution rates of the tablets.
Inhibition of glutamate decarboxylase by salicylate in vitro
Authors: McArthur N , Smith M J H
Published: April 2011

Salicylate inhibits the activity of glutamate decarboxylase from Escherichia coli by a reversible mechanism, but high concentrations of the drug denature the enzyme protein

Salicylate inhibits the activity of glutamate decarboxylase prepared from Escherichia coli and rat brain (Gould, Huggins & Smith, 1963; Gould & Smith, 1965). It was suggested that the mechanism of inhibition involved an irreversible combination of the drug with the enzyme protein. This mechanism has not been confirmed in the present work. High concentrations of salicylate denature, and lower concentrations cause a reversible inhibition of the bacterial enzyme.
The dissolution of commercial aspirin
Authors: Mitchell A G , Saville Dorothy J
Published: April 2011

Two samples of commercial aspirin showing a difference in intrinsic dissolution rate have been studied. Crystallographic examination and solubility determinations failed to reveal any difference between them. The effects of agitation and temperature on intrinsic dissolution rates showed that the samples had different thermodynamic activities and, depending on the conditions, the metastable form was capable of rapid reversion to a more stable form.
A comparison of the effects of (±)-propranolol and (+)-propranolol in anaesthetized dogs; β-receptor blocking and haemodynamic action
Authors: Barrett A M
Published: April 2011

The adrenergic β-receptor blocking activities of (±)-propranolol and (+)-propranolol have been compared in anaesthetized dogs, using isoprenaline as the agonist. (+)-Propranolol possessed less than one fiftieth the potency of (±)-propranolol. Intravenous (±)-propranolol (0·25 mg/kg) produced a six-fold increase in the isoprenaline dose ratio and significantly lowered heart rate, cardiac contractile force, ejection rate and tension time index. The same dose of (+)-propranolol had no effect on the isoprenaline dose ratio nor did it significantly alter these haemodynamic variables. Since both isomers of propranolol have equivalent membrane stabilizing properties it was concluded that the haemodynamic effects of (±)-propranolol at this dose level were due to specific β-blockade and not to any “quinidine-like” properties. Higher doses of (+)-propranolol (1·25 mg/kg) significantly reduced heart rate and cardiac contractile force whilst increasing atrio-ventricular conduction time without raising the threshold to isoprenaline. There was no effect on ejection time, mean ejection rate or tension time index. Extremely high doses of (+)-propranolol slightly raised the isoprenaline dose ratio in intact dogs but not after vagal section. The arithmetic difference between the effects of equivalent doses of (±)-propranolol and (+)-propranolol was approximately constant. The findings suggest that (±)-propranolol reduces cardiac work by blocking the sympathetic drive to the heart at doses up to 0·2 mg/kg (the usual clinical dose range) and that direct depression of the mycardium only occurs at doses well above this.
Comparison of bromisoval and carbromal in the rat
Authors: Rauws A G
Published: April 2011

Distribution experiments in vitro and in vivo with bromisoval and carbromal have shown carbromal to be more lipophilic and cumulative in brain and fat tissue. The half-life of bromisoval in the rat is approximately 2·5 h, that of carbromal is longer and variable. Stimulation and inhibition experiments revealed that both drugs are metabolized and follow different patterns. Carbromal toxicity is enhanced by bromide treatment, whereas bromisoval toxicity is not. The results show that carbromal is more toxic than bromisoval for the rat.
The binding of salicylate to plasma protein from several animal species
Authors: Kucera J L , Bullock F J
Published: April 2011

A comparison has been made of the binding of salicylate to plasma from man, green monkey, rabbit, rat, dog, and guinea-pig. Since the total protein content of normal, citrated, pooled plasmas of these species was not identical, comparisons were made with samples adjusted to the same total protein concentration. The % binding to plasmas of 5·3% total protein at 50 μg of drug/ml was found to be: man, 72%; green monkey, 70%; guinea pig, 64%; rabbit, 64%; rat, 47%; dog, 45%. Results for 150 μg and 500 μg of salicylate/ml are also reported. The albumin: globulin ratio as determined by electrophoresis varied widely among the species. Fractionation of the plasmas and comparison of binding, using 3% solutions of the various albumin fractions in buffer, indicated that the low binding of dog and rat plasmas was due primarily to the low binding affinity of the albumins. Adequate characterization of plasma samples is needed when comparative binding studies are made.
Possible oestrogenic and anti-androgenic effects in rats treated with the oral hypoglycaemic agents tolbutamide and acetohexamide
Authors: Saad Samir Fahmy
Published: April 2011

Tolbutamide has an oestrogenic activity; when administered in four oral daily doses of 125, 250 and 500 mg/kg to ovariectomized young rats, it significantly increased their uterine weight. Tolbutamide, when administered in five oral daily doses to castrated young male rats, decreased the weight of the prostatic tissue; the effect was significant with a dose of 250 mg/kg. Acetohexamide in oral doses of 125, 250 and 500 mg/kg, had no significant effect either on the prostatic or the uterine weight.
Interaction between histamine and monoamine oxidase inhibitors
Authors: Allen G S , Rand M J
Published: April 2011

The monoamine oxidase inhibitors tranylcypromine, nialamide and iproniazid potentiated the actions of histamine on the blood pressure of the cat and on the tracheo-bronchial muscle of the guinea-pig. These findings may have relevance to side-effects of treatment with monoamine oxidase inhibitors.
Central and peripheral monoaminergic membrane-pump blockade by some addictive analgesics and antihistamines
Authors: Carlsson Arvid , Lindqvist Margit
Published: April 2011

The ability of various analgesics and antihistamines to block the amine-uptake mechanism (the so-named membrane pump) of central and peripheral monoamine-storing neurons was investigated in mice. Activities indicating such blockade were observed within both groups but did not seem to correlate with analgesic or antihistaminic activity. The antihistamine chlorpheniramine proved remarkably potent on central 5-hydroxytryptamine neurons.
Stabilization of oil-in-water emulsions by non-ionic detergents: the effect of polyoxyethylene chain length
Authors: Elworthy P H , Florence A T
Published: April 2011

The stability of emulsions of anisole and chlorobenzene in water has been estimated by following microscopically the size distribution of emulsions as a function of time. The effect of increasing the length of the polyoxyethylene glycol chain of the hexadecyl ether non-ionic stabilizers from three units to nine units was determined. Electrophoretic measurements indicated that the higher stability obtained on increasing the glycol chain length is not due to an increasing surface potential: it is ascribed to an entropic effect. Stability data are tabulated as rates of coalescence (s−1) and results are presented relating these rates to zeta-potential, surface concentration and polyoxyethylene chain length. The results are discussed qualitatively and compared with the results obtained with cetomacrogol 1000 (Elworthy & Florence, J. Pharm. Pharmac., 1967, 19, 140S).
Stabilization of oil-in-water emulsions by non-ionic detergents: electrical and entropic contributions to stability
Authors: Elworthy P H , Florence A T
Published: April 2011

Calculations of the attractive and repulsive forces between globules of anisole and chlorobenzene in the presence of non-ionic detergents of varying polyoxyethylene chain length are presented. The equations of the Derjaguin-Landau-Verwey-Overbeek theory are used and the effect on the attractive potential of the adsorption of stabilizer onto the particle is taken into account. The adsorbed film was found to increase the attractive forces between the particles, VA. In the previous paper (Elworthy & Florence, J. Pharm. Pharmac., 1969, 21, 70) it was shown that the electrical contribution to stability is a secondary stabilizing factor. More quantitative estimates of this contribution have been made. The entropic repulsion has been calculated using an equation of Ottewill & Walker. The energy-distance diagrams are discussed in the light of the experimental results presented in the previous paper.
The alkaloids of the leaves of Mitragyna inermis (Willd.) O. Kuntze
Authors: Shellard E J , Sarpong K
Published: April 2011

The leaves of Mitragyna inermis (Willd.) O. Kuntze have been examined for alkaloids and shown to contain routundifoline, isorotundifoline, rhynchophylline, isorhynchophylline, ciliaphylline, rhynchociline, speciophylline, a small amount of uncarine F, mitraciliatine and traces of a second indole alkaloid which appears to be of the corynanthine type. There is also a polar compound present, Dragendorff positive, which remains on the base line when subjected to thin-layer chromatography with the usual solvent systems used for the mitragyna alkaloids.
Kinetics of buccal absorption of some carboxylic acids and the correlation of the rate constants and n-heptane:aqueous phase partition coefficients
Authors: Beckett A H , Moffat A C
Published: April 2011

A simple model for the buccal absorption of some carboxylic acids is proposed. This model has been used, in conjunction with an analogue computer, to determine the rate constants of buccal absorption of ten acids from solutions of pH 4·0 using a single subject. These rate constants gave a positive correlation with the logarithms of previously determined n-neptane:0·1 N hydrochloric acid partition coefficients (correlation coefficient 0·89).
Potentiation of the effects of noradrenaline and of sympathetic stimulation of the perfused rat caudal artery by angiotensin
Authors: Nicholas T E
Published: April 2011

The isolated perfused caudal artery of the rat develops tachyphyllaxis rapidly to the direct constrictor action of angiotensin but not towards the potentiation of responses to submaximally effective periarterial stimulation or to noradrenaline. These potentiations persist in the presence of maximally effective concentrations of cocaine, are unaffected by increased sodium concentration and are enhanced by raised concentrations of calcium. Thus, angiotensin potentiates the effects of sympathetic nervous activity by an influence on the role of calcium in the contractile process. Hydrochlorothiazide did not affect arterial tone, the responses of the artery, or the potentiation to noradrenaline caused by angiotensin.
Potentiometric determination of sodium using a sodium ion responsive glass electrode
Authors: Pearson J T , Elstob Catherine M
Published: April 2011

A study to assess the feasibility of using a sodium ion responsive glass electrode in conjunction with a saturated calomel reference electrode to measure the sodium ion concentration of a wide range of electrolyte solutions used in clinical medicine has shown that the method is capable of giving results which are within acceptable limits. Direct measurement of solutions containing sodium chloride is possible by reference to a calibration based on the potential produced by the electrode pair as a function of pNa+ defined as -log10 sodium ion concentration. For the measurement of the sodium content of solutions of sodium salts of weak acids and mixed solutions of electrolytes and dextrose it is necessary to use a calibration carried out in a buffer system (0·5M triethanolamine + hydrochloric acid to pH 7) and to dilute the preparations with buffer before measurement. It is also necessary to buffer dextrose and sodium chloride injection before measurement due to the effect of decomposition of dextrose during sterilization causing a shift in pH which must be corrected before making a determination. The advantages of the potentiometric method over conventional flame photometric and titrimetric methods are discussed and a brief review of the literature given, to indicate the applications of specific ion electrodes.
The absorption, distribution and excretion of pentazocine in man after oral and intravenous administration
Authors: Beckett A H , Taylor J F , Kourounakis P
Published: April 2011

Gas-liquid chromatography is a sensitive technique for the analysis of pentazocine in biological samples. Dose for dose, the concentration in blood and the urinary excretion rate of pentazocine are much lower after oral administration than after intravenous administration. The recovery of the unchanged drug in faeces is low whether it is given by mouth or intravenously.
Structural specificity for inhibition of [14C]-5-hydroxytryptamine uptake by cerebral slices
Authors: Carlsson A
Published: April 2011

Cerebral slices were prepared from mice pretreated with reserpine and nialamide. The slices were incubated for 40 min at 37° in a Krebs-Henseleit solution equilibrated with 5% carbon dioxide in oxygen and containing [14C]-5-hydroxytryptamine. An uptake, dependent on energy metabolism and temperature, was observed. The uptake was blocked by tricyclic antidepressants, the order of activity being chlorimipramine > imipramine > desipramine. For 50% inhibition 0.03 μg/ml of chlorimipramine was required, when added to the suspension medium, or 1 mg/kg, when injected intraperitoneally 20 min beforehand. Comparison with earlier experiments using different experimental techniques appears to justify the conclusion that the evidence obtained represents the uptake mechanism of cerebral 5-hydroxytryptamine neurons.
Corticosteroid-collagen interaction in vitro: fibril formation from collagen solutions
Authors: Cooper D R , Kanfer I , Price C H
Published: April 2011

The disodium phosphate ester salts of betamethasone, prednisolone and hydrocortisone dissolved in a fibril initiating buffer accelerated the precipitation of fibrils from saline solutions of acid-soluble collagen at pH 7.0, when compared with the rate for the initiating buffer alone at the same pH. Without the initiating buffer these corticosteroids also precipitated collagen fibrils, but at a slower rate than when the initiating buffer was present. A relation has been found between the substitution of active groups on the basic steroid nucleus and the rate of collagen fibril formation from solution. Electron microscope examination of the fibrils precipitated by these corticosteroids showed that they corresponded to normal collagen fibrils in appearance and in having the characteristic repeat period of 60–70 nm.
Theoretical changes in drug distribution resulting from changes in binding to plasma proteins and to tissues
Authors: Curry Stephen H
Published: April 2011

Concentrations of chlorpromazine fluctuate in the plasma of dogs and man after intravenous doses. The possibility that the fluctuations could arise from movement of the drug between tissue and plasma stores is examined theoretically. Calculations show that small changes in protein binding of drugs in plasma and tissues could cause redistribution of highly bound drugs between tissues and plasma. Redistribution would be greatest after changes in tissue binding of highly bound drugs. Fluctuations in chlorpromazine concentrations could be caused in this way.
The effect of magnesium ions and Tris buffer on the uptake of cetyl trimethyl ammonium bromide by Escherichia coli
Authors: Salt W G , Wiseman David
Published: April 2011

The uptake of CTAB by E. coli from a glucose-free mineral salts medium occurs in two distinct phases. Increasing the magnesium ion content of the suspending medium emphasizes the diphasic nature of the isotherm. The primary phase is extended and the height of the “saturation” plateau of the secondary phase, as a function of CTAB uptake, is reduced. The CTAB uptake isotherm for E. coli suspended in water is not obviously diphasic and the maximum amount of CTAB taken up by the cells at “saturation” is less than that in medium. The height of this plateau is influenced by Tris buffer, an increase in the Tris concentration increasing the maximum CTAB uptake. A method for the rapid screening of uptake isotherms based on turbidity changes is also discussed.
Analysis of the action of m-tyrosine on blood pressure in the conscious rat: evidence for a central hypotensive effect
Authors: RUBENSON ALLAN
Published: April 2011

Mean arterial blood pressure was recorded through indwelling arterial catheters in conscious normotensive rats. dl-m-Tyrosine, 400 mg/kg, was given intraperitoneally alone and after pretreatment with two inhibitors of dopa decarboxylase [dl-α-hydrazino-α-methyl-β-(3,4-dihydroxyphenyl) propionic acid (MK 485) or N1-(dl-seryl)-N2-(2,3,4-trihydroxybenzyl)hydrazine (Ro 4–4602)]. dl-m-Tyrosine alone produced a hypertensive response, but after MK 485 it caused a significant lowering of blood pressure after 5–7 min and after Ro 4–4602 (400 + 200 mg/kg) it had no significant influence on blood pressure. The hypotensive response to dl-m-tyrosine was not influenced by the central dopamine receptor blocking agent spiroperidol (0·1 mg/kg) or by pretreatment with the tyrosine hydroxylase inhibitor H 44/68 (250 mg/kg). However, the depressor action could be completely inhibited after depletion of central catecholamines by α-methyl-m-tyrosine, 400 + 400 + 200 mg/kg, in combination with H 44/68, 250 mg/kg. Further, the depressor action was abolished by the dopamine β-hydroxylase inhibitor bis (4-methyl-1-homo-piperazinyl-thiocarbonyl) disulphide (FLA-63) 40 mg/kg. In correlative biochemical experiments the concentrations of the decarboxylation products of m-tyrosine were measured in brain and heart. dl-m-Tyrosine alone produced an accumulation of m-tyramine and m-octopamine in these tissues. MK 485 + m-tyrosine substantially reduced the levels of m-tyramine and m-octopamine in the heart, but their accumulation in brain was largely unaltered. The results suggest that when decarboxylation of dl-m-tyrosine occurs in both the central and peripheral nervous system, there is a pressor action. When decarboxylation occurs mainly in the central nervous system there is a hypotensive response which is associated with accumulation of decarboxylation products of m-tyrosine.
The effect of the histidine decarboxylase inhibitor brocresine (NSD-1055) on gastric acid secretion in rats
Authors: BECKER M , SEWING K-FR
Published: April 2011

The effect of the histidine decarboxylase inhibitor brocresine (NSD-1055) given by mouth, intraperitoneally or intravenously on tetragastrin-, histamine- and bethanechol-stimulated gastric acid secretion was examined in rats. Intravenous injection of brocresine slightly reduced the tetragastrin-stimulated secretion. Histamine-stimulated secretion was markedly increased by both intraperitoneal and intravenous injection of brocresine but it had no effect on the bethanechol-stimulated secretion. It was concluded that either histidine decarboxylase is not effectively inhibited by brocresine or any inhibition induced does not affect gastric acid secretion. The enhanced histamine-stimulated secretion points towards an inhibition of diamine oxidase by brocresine.
Effects of papaverine and eupaverin on calcium uptake by isolated sarcoplasmic vesicles
Authors: CARPENEDO F , TOSON G C , FURLANUT M , FERRARI M
Published: April 2011

Papaverine and eupaverin increase the rate of uptake of calcium by sarcoplasmic vesicles isolated from rabbit white skeletal muscle. The degree of activity of the above drugs is clearly affected by changes of ATP, oxalate and Ca2+ concentrations. The results are discussed in view of present knowledge about the effects of papaverine-like drugs upon muscular contraction.
The effect of detergent concentration on monomer activity in a non-ionic detergent solution
Authors: MACFARLANE C B , ELWORTHY P H , GYANE D O
Published: April 2011

The mono-octyl ether of hexaoxyethylene glycol has been synthesized and carefully purified using foam fractionation in the ultimate stages of the purification. Surface tension measurements of solutions of the detergent in water using a Wilhelmy plate indicate a continuing decrease in surface tension with increasing detergent concentration above the critical micellar concentration. Vapour pressure osmometry using the Mechrolab 302 substantiated the interpretation of the results in terms of the law of mass action.
The solubility of some compounds in hexadecylpolyoxyethylene monoethers, polyethylene glycols, water and hexane
Authors: CORBY T C , ELWORTHY P H
Published: April 2011

The solubilities of a series of compounds of varying polarity, i.e. decane, benzene, sulphadiazine, p-hydroxybenzoic acid, ethyl and butyl p-hydroxybenzoate and methyl anisate in cetomacrogol 1000 and hexadecyl heptaoxyethylene ether solutions, have been determined. A comparison of these results with the solubilities of these compounds in water, n-hexane and polyethylene glycol solutions gives some evidence on the mechanism of solubilization. The results show that the solubilization of these compounds is not adequately described solely on the basis of solubility into the separate regions of the micelle. The micellar solubility of the compounds was dependent on the hydrocarbon solubility and the presence of groups in the molecule which can form hydrogen bonds. Butyl paraben was found to have a higher solubility in 10% cetomacrogol solutions than either ethyl paraben or methyl anisate. The hydrophil–lipophil characteristics of the detergents with the polarity of the solubilizate molecule also affect solubilization. A non-polar molecule such as decane has a greater solubility in the more lipophilic detergent and the reverse is true of p-hydroxybenzoic acid.
Identification of the site of solubilization of various compounds by cetomacrogol
Authors: CORBY T C , ELWORTHY P H
Published: April 2011

Solubilization of some of the esters of p-hydroxybenzoic acid by cetomacrogol 1000 solutions has been investigated by ultraviolet spectrophotometry, nuclear magnetic resonance spectrometry and viscometry to provide evidence on the environment of each part of the solubilizate molecule as well as the detergent molecule. Hydration of the micelles calculated from the viscometry results, gave further evidence on the site of solubilization of the compounds. On the basis of these results and solubility results published previously it is suggested that the compounds are solubilized as follows: p-Hydroxybenzoic acid is wholly solubilized deep in the oxyethylene layer of the micelle. Ethyl p-hydroxybenzoate is solubilized mostly in the oxyethylene layer and is situated adjacent to the core: some solubilization occurs within the core. Butyl p-hydroxybenzoate is solubilized mainly at the oxyethylene-hydrocarbon junction, the phenyl ring in the oxyethylene layer and the butyl chain in the core: some solubilizate is wholly present in the core. Methyl p-methoxybenzoate: most of the compound is dissolved in the micellar core, but some is also present in the oxyethylene layer. Benzene is solubilized in a similar manner to methyl p-methoxybenzoate.
The adsorption of crystal violet by kaolin
Authors: ARMSTRONG N A , CLARKE C D
Published: April 2011

The uptake of crystal violet on kaolin was examined over a pH range of 2·5 to 9·5, adsorption showing an increase with pH. The attainment of equilibrium between adsorbate and adsorbent is shown to be a two-stage process, the first stage being synchronous with the release of magnesium from the kaolin lattice. Evidence is presented that the major mechanism of adsorption is by electrostatic charges arising from cation replacement in the clay lattice, and that charges arising from the amphoteric nature of the aluminium atom of kaolin make little contribution to the overall adsorptive process.
The kinetics of crystallization of potassium bromide from aqueous solution
Authors: RIDGWAY K , AULTON M E
Published: April 2011

The densities of aqueous solutions of potassium bromide have been determined as a function of concentration and temperature up to saturation at temperatures between 10 and 50°. The saturation line and nucleation were studied, over the same temperature range, in a circulatory crystallizer with continuous concentration monitoring. Small quantities of seed crystals were grown under different degrees of supersaturation and at different temperatures, so that the mass transfer coefficients and the activation energy for deposition from solution could be measured. The activation energy of the crystallization process was 100·9 kJ mol−1, indicating that the rate-determining step was the incorporation of KBr on to the crystal lattice. Rapidly-grown crystals might thus be expected to be softer, and this proved to be so.
Alkaloids from two Nigerian species of Fagara
Authors: FISH F , WATERMAN P G
Published: April 2011

Skimmianine, chelerythrine, nitidine, 1-hydroxy-2,3-dimethoxy-10-methylacridan-9-one and 1-hydroxy-3-methoxy-10-methylacridan-9-one have been isolated from the root and stem barks of Fagara rubescens. Using thin-layer chromatography and high voltage electrophoresis, a comparison of the chloroform-insoluble quaternary alkaloids of this species has been made with those from F. leprieurii. The distribution of the alkaloids within the barks and the chemotaxonomic significance of the alkaloids in the two species are discussed.
The in vitro evaluation of gelatin coacervate microcapsules
Authors: NIXON J R , WALKER S E
Published: April 2011

Microcapsules of sulphadiazine have been prepared by the simple gelatin coacervation technique, using sodium sulphate as coacervating agent. The free flowing microcapsular material was hardened with formalin. There is no direct relation between particle size and sulphadiazine concentration nor between different starting gelatin percentages. The effects on size of hardening time, temperature and sampling time are small. In vitro dissolution studies show that first order release characteristics are exhibited by all the hardened materials. Temperature and pH effects indicate the dissolution of the sulphadiazine itself to be the controlling step rather than the rate of diffusion through the microcapsule wall.
Further studies on the effect of additives on the release of drug from hard gelatin capsules
Authors: NEWTON J M , ROWLEY G , TÖRNBLOM J-F V
Published: April 2011

An experiment based on a 33 design has been undertaken to establish the effect on drug release from capsules produced by adding lactose (0, 10 and 50%), magnesium stearate (0, 1 and 5%), and sodium lauryl sulphate (0, 1 and 10%) to a 76–105μm particle size fraction of ethinamate filled into capsules at a high and low packing density. Statistical analysis of the results indicated the presence of 2nd order interaction at all time intervals and for both sets of capsule fill weights. This signifies that the effect produced by each additive is dependent on the presence and the level of the other two additives. The interaction limits the conclusions that can be drawn about the main factors of diluent, lubricant and wetting agent, but the indications are that (a) 10% diluent reduces drug release, whereas 50% produces enhanced release; (b) the presence of 1% sodium lauryl sulphate is sufficient to enhance drug release; (c) the additive effects are independent of the capsule packing density.
Hydrophobic bonding in soap-stabilized emulsions
Authors: DAVIS STANLEY S
Published: April 2011

The rheological properties of emulsions stabilized by potassium laurate have been measured at different temperatures and in the presence of urea to assess the validity of the concept of aggregation through hydrophobic interactions. The elasticity of the systems, as measured by a Rheogoniometer, increased with increased temperature and decreased with added urea. These results are entirely consistent with hydrophobic bonding. The mechanism of bonding is discussed in terms of interfacial hydrolysis, complex condensed films of acid soap, and polymolecular adsorption of surfactant at the oil-water interface.
Digital filters in the evaluation of titration curves
Authors: PERKS F , GLENN A L
Published: April 2011

The shape of a titration curve contains useful information, which may be extracted in terms of orthogonal polynomial coefficients. In this way, it is possible to (i) distinguish a monobasic acid from a polybasic acid, having groups of closely similar strength; (ii) detect acid-base impurities in acids and bases, and (iii) study medium effects. The choice of polynomial, range, number of points and experimental conditions are discussed. Using twelve point polynomials and equipment of modest performance, the Pi coefficient (for the central half of a monobasic acid titration curve) can be measured with a relative standard deviation of 0·58.
Computer analysis of the relation between tablet strength and compaction pressure
Authors: NEWTON J M , ROWLEY G , FELL J T , PEACOCK D G , RIDGWAY K
Published: April 2011

The load necessary to fracture lactose monohydrate tablets under diametral compression has been determined using an Instron physical testing instrument, so that true tensile failure was obtained in all cases, leading to improved reproducibility. Four ranges of tablet thickness were examined at 12·7 mm diameter. All tablets gave a linear increase of breaking load with compaction pressure up to 310 MN/m2. Expressing the tablet strength as the breaking load gave a separate regression line for each range of tablet thickness, whereas the use of tensile strength provided a common regression line, within given statistical limits, for all but the lowest range of tablet thickness. The fact that such a correlation is possible shows that the tensile strength is a property of the “as compacted” material and provides a new and useful parameter to maintain constancy of properties when tablet size is changed.
The actions of histamine and prostaglandins F2α and E2 on pulmonary vascular resistance of the lung of the guinea-pig
Authors: OKPAKO D T
Published: April 2011

In the guinea-pig isolated perfused lung, prostaglandin F2α (PGF2α) and histamine increased, and prostaglandin E2 (PGE2) decreased, resistance to fluid flow. PGF2α and histamine caused contractions of the pulmonary artery circular muscle preparation while PGE2 inhibited contractions caused by other agonists. It was concluded that the changes in resistance to fluid flow caused by the three agents was partly or wholly due to their direct action on pulmonary vascular tissue. Mepyramine abolished the pressor response to histamine but had no effect on the pressor response to PGF2α. Furthermore, there was no evidence of the involvement of adrenergic mechanisms in the action of the prostaglandins. It is suggested that PGF2α probably plays a role in the pulmonary vasoconstriction caused by anaphylaxis in guinea-pigs pretreated with mepyramine.
The effect of morphine pretreatment on the sensitivity of mouse and guinea-pig ileum to acetylcholine and to morphine
Authors: HAYCOCK VIVIEN K , REES J M H
Published: April 2011

Guinea-pigs and mice were subjected to morphine pretreatment for at least 14 days culminating in subcutaneous injections of 1 g/kg daily in 2 divided doses. In mice, tolerance to the effects of morphine on gastrointestinal propulsion had developed by the end of the pretreatment course. The sensitivity to acetylcholine of the ilia from pretreated animals and the effects of morphine on transmural stimulation were compared with the ilia from normal animals. Ilia from pretreated guinea-pigs were marginally more sensitive to frequency of stimulation but significantly less sensitive to the depressant effect of morphine than ilia from normal animals. There was no significant difference in the sensitivity to acetylcholine. There was a highly significant decrease in sensitivity to morphine of ilia from pretreated mice, but this also was not associated with any alteration in sensitivity to acetylcholine. It is concluded that on the isolated ileum preparation the development of tolerance to morphine is not associated with an increased sensitivity to the transmitter whose release morphine inhibits.
Observations on the interactions between desipramine and reserpine on adrenergic transmission in the rat
Authors: COTILLO P , BONACCORSI A
Published: April 2011

The time course of the impairment of the adrenergic transmission induced by reserpine has been examined on the inferior eyelid of the rat pretreated with desipramine. Desipramine given before reserpine is able to counteract, in a dose-dependent manner, the impairment induced in the first hours after reserpine. On the contrary, desipramine has only a limited effect, not dose-dependent, when given after the reserpine treatment.
Pharmacokinetics of absorption, distribution and elimination of fenfluramine and its main metabolite in man
Authors: BECKETT A H , SALMON J A
Published: April 2011

Previously reported data (Beckett & Brookes, 1967) for the excretion of (±)-fenfluramine and its main metabolite, norfenfluramine, have been examined pharmacokinetically using an analogue computer. A three compartment open model was proposed to simulate the biological processes with one peripheral compartment rapidly equilibrating with the central compartment and the second (tissue) compartment only slowly attaining equilibrium. Good agreement between experimental and computed data was obtained, although marked inter-subject variation was recorded. This was attributed to inter-subject differences in the three body compartments. Differences between the pharmacokinetic parameters obtained after oral and intravenous administration of fenfluramine indicated that the drug was significantly N-dealkylated in the intestine or on a first-pass through the liver.
Partition coefficients of salicylic acid between water and the micelles of some non-ionic surfactants
Authors: COLLETT J H , WITHINGTON R
Published: April 2011

Partition coefficients of ionized and unionized salicylic acid molecules between water and the micelles of several non-ionic surfactants have been determined. Those of unionized molecules decreased with decreasing length of the surfactant alkyl chain and with increasing length of the surfactant polyoxyethylene chain. Ionized salicylic acid partitioned to a significant extent only into those surfactants having more than approximately 44 oxyethylene units in their hydrophile. The findings are discussed in terms of their biopharmaceutical significance.
Relation between cation and lipid content of cell walls of Pseudomonas aeruginosa, Proteus vulgaris and Klebsiella aerogenes and their sensitivity to polymyxin B and other antibacterial agents
Authors: BROWN M R W , WOOD SANDRA M
Published: April 2011

Sensitivity to polymyxin correlated with amount of phospholipid in wall fractions of Pseudomonas aeruginosa, Proteus vulgaris and Klebsiella aerogenes and to a lesser extent with wall cation. The affinity of polymyxin for phospholipid from P. vulgaris and P. aeruginosa was the same.
Scopolia lurida, Dunal; the structure of the leaves and stem
Authors: MILLS DAVID E , JACKSON BETTY P
Published: April 2011

The aerial parts of Scopolia lurida contain large quantities of tropane alkaloids and are a possible source of hyoscyamine and hyoscine. The leaves and stems are very similar to those of Atropa belladonna but they can be distinguished by certain microscopical characters; these include the presence of branched covering trichomes on the leaves and stems of Scopolia lurida and the absence of idioblasts containing microsphenoidal crystals of calcium oxalate from the leaf lamina.
Adaptation to the natriuretic actions of hydrochlorothiazide, frusemide and amiloride, by rats
Authors: ILETT K F , LOCKETT MARY F
Published: April 2011

Rats treated thrice daily with maximally natriuretic doses of amiloride or of frusemide showed a markedly diminished natriuretic response (adapted) by the third day and complete adaptation to hydrochlorothiazide by the fifth day of treatment. Normal rats supplied with 0.7 % NaCI as drinking fluid and adrenalectomized rats maintained by either a high salt intake or by injections of doca could not adapt to the natriuretic effects of hydrochlorothiazide. There was no adaptation to the effects of these diuretics on K+ excretion. Treatment of rats for eight successive days with amiloride, frusemide or hydrochlorothiazide caused significant elevation of the juxtaglomerular index and hyperactivity in the zona glomerulosa of the adrenal. Treatment for eight days with spironolactone did not produce these changes. The in vitro production of aldosterone was significantly increased in glands taken from animals pretreated for eight days with hydrochlorothiazide: spironolactone did not influence this synthesis. Plasma concentrations of corticosterone were unaffected by eight days of exposure to hydrochlorothiazide, were raised by this exposure to frusemide and were lowered by amiloride. It is considered that the reninangiotensin-aldosterone system plays a rôle in adaptation, over days, to the natriuretic effects of sulphonamide and probably other natriuretic diuretics, in the rat.
Effect of β-adrenoceptor antagonists on the decline of the chronotropic response to isoprenaline
Authors: FENYVESI T , GEORGE C F , DOLLERY C T
Published: April 2011

The effect of three β-adrenoceptor antagonists (propranolol, practolol and H 35/25*) have been investigated on the decline of the tachycardia produced by intravenous doses of isoprenaline. Propranolol (0.5 mg/kg laevo-isomer) caused a significant increase in the rate of decline from 17.2 to 36.5 beats/min. Practolol (2 mg/kg), H 35/25 (2 mg/kg) and the combination of the two did not influence the rate of decline. Only propranolol caused a change in the slope of the isoprenaline heart rate dose-response curve; the observed increase of this slope is the probable cause of the change in rate of decline of the heart rate response.
Physicochemical properties of spray-dried agglomerated particles of salicylic acid and sodium salicylate
Authors: KAWASHIMA Y , MATSUDA K , TAKENAKA H
Published: April 2011

Aqueous slurries of salicylic acid and sodium salicylate, containing various kinds of binder, namely gum arabic, gelatin, polyvinyl alcohol, carboxymethylcellulose, methylcellulose, polyvinylpyrrolidone, tragacanth and sodium alginate, were spray dried using a centrifugal wheel atomizer. Almost all the spherical dried products were free flowing microgranules, although formulations including gelatin or polyvinyl alcohol proved to be difficult due to agglomeration. Particle properties such as diameter, true density, sphericity and surface area were measured, all of these being strongly influenced by the concentrations of sodium salicylate and binder. The surface topography of the products was studied with a scanning electron microscope. Granules bound with gum arabic and polyvinylpyrrolidone had smooth surfaces without holes or craters. Analysis of the X-ray diffraction patterns and the infrared absorption spectrum of products showed that these granules still contained both salicylic acid and sodium salicylate, in contrast to granules prepared using other binders, where only sodium salicylate remained, the salicylic acid having sublimed. They are microcapsules containing salicylic acid and sodium salicylate of grain size of about 20–80 and 13–17 nm respectively, and amorphous contents of about 50–80%. The thickness of the encapsulating film was 1–3 μm. The change in appearance of a drying slurry droplet is discussed and two typical drying processes are described.
Structure of an iron-dextran complex
Authors: COX J S G , KENNEDY G R , KING J , MARSHALL P R , RUTHERFORD D
Published: April 2011

An iron-dextran complex* from which most of the uncomplexed dextran present had been removed by ultracentrifugation has been examined by electron microscopy and by gel chromatography. In the first technique, freeze-drying to prevent aggregation and distortion followed by shadow-casting with platinum-iridium gave a clear impression of the particulate nature of the complex. The chromatographic experiments on Sephadex G200 confirmed the particle size and showed that the particle size distribution was not wide. The iron-dextran component is thus seen as a small particle of approximately 3 nm diameter when examined only as the FeOOH ‘core’ and of approximately 13 nm diameter when the attached dextran is also observed. A structural model of the particle is presented with the dextran attached by the terminal metasaccharinic acid units to the FeOOH component.
Application of orthogonal functions to spectrophotometric analysis: The Δpj method
Authors: ABDINE H , WAHBI A M , KORANY M A
Published: April 2011

A general method is outlined for the use of orthogonal functions to eliminate interference in differential spectrophotometric analysis. The method is particularly useful when (i) the optimum conditions of the ΔA method are not fulfilled and (ii) the irrelevant absorption is linearly dependent upon the spectrum of the pure compound or its shape is completely unknown. The results obtained for the determination of clemizole in tablets are encouraging and suggest that the method warrants a careful study over a wide field of applications.
The antinociceptive activities of oxotremorine, physostigmine and dyflos
Authors: COX B , THA S J
Published: April 2011

Oxotremorine and physostigmine caused dose-related increases in the hot plate reaction time (HPRT) of mice, but dyflos did not. Physostigmine did not potentiate a low dose of oxotremorine (0.025 mg/kg) in the HPRT test, but some potentiation of higher doses of oxotremorine (0.05 and 0.1 mg/kg) may have occurred. Dyflos did not potentiate any dose of oxotremorine. Physostigmine and dyflos inhibited mouse brain cholinesterase but oxotremorine was without effect. The relation between change of HPRT and cholinesterase inhibition was different for physostigmine and dyflos.
α-Adrenoceptors of aortae from genetically hypertensive rats: reaction with 2-halogenoethylamines
Authors: JANIS R A , TRIGGLE D J
Published: April 2011

The responses of aortic rings from adult spontaneously hypertensive and Carworth normotensive Wistar rats to noradrenaline were compared. The former developed slightly more tension at low, and markedly less tension at high concentrations (> 10−8m) of noradrenaline. The α-adrenoceptors of these tissues were probed using 2-halogenoethylamines to compare quantitatively α-adrenoceptors in normotensive and hypertensive tissue. The kinetics of the recovery of response to noradrenaline from the short-lived antagonism produced by NN-dimethyl-2-bromo-2-phenylethylamine were identical in aortae from both strains of rat. The rate of recovery of response was the same as the rate of loss of tritium from the tissues, suggesting the absence of spare receptors in rat aorta. An estimation of the number of α-adrenoceptors in aortic tissue did not show a difference between normotensive and hypertensive tissues. Evidence is presented that 2-halogenoethylamines react at two kinetically distinguishable sites in rat aorta. The rates of return of response to noradrenaline after receptor blockade with N-(2-bromoethyl)-N-ethyl-N-1-naphthylmethylamine (SY-28) in tissues pretreated with NN-dimethyl-2-bromo-2-phenylethylamine were the same in aortic smooth muscle from both strains of rat. No significant difference was found in the reactions of 2-halogenoethylamine α-adrenoceptor antagonists in aortic tissue from either strain of rat.
The influence of some aliphatic alcohols on the enzymic hydrolysis of methyl hippurate
Authors: DICKINSON N A , REES JUDITH A , COLLETT J H
Published: April 2011

The hydrolysis of methyl hippurate under the influence of α-chymotrypsin and some aliphatic alcohols has been investigated. Methanol, ethanol, n-propanol, n-butanol and n-pentanol were found to inhibit the rate of hydrolysis. The dissociation constants KI for an assumed enzyme-inhibitor complex and KSI for an assumed (enzyme-substrate)-inhibitor complex have been evaluated. In all cases KSI > KI with a ratio of 1·1 to 1 for methanol and 2 to 1 for other alcohols. From the relation between the pK values it is calculated that the free energy change accompanying loss of bound water from each -CH2- group was -2mD1 kJ mol−1.
Effects of narcotic analgesics on contractions of the chick isolated, innervated oesophagus
Authors: BOWMAN W C , BUWEMBO J B
Published: April 2011

The effects of the analgesics, morphine, diacetylmorphine, etorphine, methadone, pethidine, propoxyphene, pentazocine, cyclazocine and phenazocine were studied on contractions of the isolated innervated oesophagus of chicks. All of the analgesics depressed contractions of the oesophagus evoked by coaxial stimulation, the effect being greater the lower the frequency of stimulation. Tachyphylaxis and cross tachyphylaxis to and between the drugs developed rapidly. During the depressant effect on the electrically evoked contractions, responses to acetylcholine and 5-hydroxytryptamine were not depressed, except in the cases of pethidine, propoxyphene and pentazocine which depressed responses to acetylcholine. Nalorphine added during the depressant action antagonized the effects of morphine, diacetylmorphine, etorphine, methadone and phenazocine, partially antagonized those of pethidine and propoxyphene but did not antagonize those of pentazocine or cyclazocine.
Gas-liquid chromatographic estimation of tolbutamide and chlorpropamide in plasma
Authors: PRESCOTT L F , REDMAN D R
Published: April 2011

An improved method for the gas-liquid chromatographic estimation of tolbutamide and chlorpropamide in plasma is described. The drugs are extracted into toluene, back-extracted into alkali and methylated with dimethylsulphate. The methylated derivatives are extracted into n-hexane, concentrated by evaporation and chromatographed on 3·8% UC W98 or 1% Carbowax 20M columns. The standard deviation of replicate analyses of plasma samples containing 20–100 μg/ml of either drug was about 4%. There is no interference from known metabolites of tolbutamide or chlorpropamide.