bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cooling as a possible method for increasing the flowability of certain pharmaceutical and other powders
Authors: Onyekweli A O , Pilpel N 
Published: April 2011

Abstract
Measurements have been made of the rates of flow under gravity of powdered sugars and of fatty acids through circular orifices at temperatures between −25 and 110 °C. The flow rates decrease considerably as the powders are heated; conversely they increase as the powders are cooled from a high ambient temperature of 40 to −25 °C. The results are ascribed to changes in the cohesiveness of the powders caused by softening and plastic deformation of particles at elevated temperatures. Lactose, paracetamol and griseofulvin granule formulations have been reported to show similar effects and the possibility is discussed of using cooling to increase the flowability of particular powders in pharmaceutical production. The rates of flow of the powders are given by the expression
where W is the flow rate in g min−1, Do is the orifice diameter in cm, ρ is the particle density in g cm−3, g is the gravitational constant, and A and n are numerical terms which depend on temperature and particle size.
Accelerated storage tests on pharmaceutical products: effect of error structure of assay and errors in recorded temperature
Authors: Davies O L , Budgett D A 
Published: April 2011

Abstract
The likely error structure for accelerated shelf-life studies is discussed. How to fit the Arrhenius relationship in the presence of this structure is shown and it is concluded that test potencies between 20% and 50% are likely to provide most information. The effect of temperature errors on the estimation of shelf-life is also considered.
Photosensitization by drugs: photolysis of some chlorine-containing drugs
Authors: Moore Douglas E , Tamat Swasono R 
Published: April 2011

Abstract
Irradiation with ultraviolet light of chlorpromazine, prochlorperazine, frusemide or hydrochlorothiazide in either aqueous or methanol solution yielded free chloride ion. Potentiometric methods were used to detect one mol of chloride ion produced per mol of drug irradiated in deoxygenated solution, with a concomitant equimolar appearance of hydrogen ion. Saturation of the solutions with oxygen strongly inhibited the photolysis reaction in methanol but only partially inhibited the production of Cl− and H+ in aqueous solution. The oxidation of 2,5-dimethylfuran is photosensitized by these drugs more effectively in methanol compared with aqueous solution. The photochemical behaviour is consistent with a photo- dissociative process occurring predominantly in methanol while photoionization predominates in aqueous media. No chloride ion was detected after extended irradiation of Chlortetracycline, demeclocycline, chlordiazepoxide and hexachlorophane. The photolability of the chlorine in the compounds tested correlated with their ability to photosensitize oxidation by the Type I (free radical) mechanism.
Inhibitors of α-chymotrypsin derived from cephalosporins: structure-activity relationships
Authors: Hachim B , Smith H J 
Published: April 2011

Abstract
Cephalothin and certain other cephalosporins are irreversible inhibitors of α-chymotrypsin in near neutral media. The active inhibiting species is slowly generated in small yield from cephalothin in aqueous solution. Structure-activity studies for 37 other cephalosporins and related compounds establish that inhibitors of the enzyme require in the parent cephalosporin molecule a 7-acyl substituent containing a flat area in the form of an aromatic or heterocyclic ring together with a 3-acetoxymethyl or other substituent which is labile to water. The inhibitory species is considered to be the oxazolinone derived from the corresponding cephalossporoic acid.
Rotational behaviour elicited by 5-HT in the rat: evidence for an inhibitory role of 5-HT in the substantia nigra and corpus striatum
Authors: James Thomas A , Starr Michael S 
Published: April 2011

Abstract
Unilateral intranigral microinjection of 5-HT or Wy 25093, a selective inhibitor of 5-HT uptake, elicited ipsiversive circling and a fall in striatal dopamine (DA) turnover. Conversely intranigral methysergide or unilateral lesions of the raphe-nigral 5-HT pathway produced contraversive turning and/or increased DA turnover. Both types of behaviour were accentuated by nialamide and attenuated by haloperidol. Caudate injections of 5-HT or Wy 25093 provoked contraversive turning which was increased by nialamide and hyoscine, partially diminished by haloperidol and antagonized by eserine. Ipsiversive circling was induced by intracaudate methysergide, which was potentiated by nialamide and eserine, unaffected by haloperidol and depressed by hyoscine. It is proposed that 5-HT normally subserves an inhibitory function both in the substantia nigra and corpus striatum.
Comparison of the effects of the stereoisomers of fenfluramine on the acetylcholine content of rat striatum, hippocampus and nucleus accumbens
Authors: Consolo S , Ladinsky H , Forloni G L , Tirelli A S , Garattini S 
Published: April 2011

Abstract
The (+)- and (-)- isomeric forms of fenfluramine were compared for their effects on rat brain area acetylcholine (ACh) content. The drugs showed similar patterns in increasing ACh content in the accumbens and hippocampus and in being ineffective in the brainstem. The actions differed in the striatum where the (+)-form markedly increased ACh content while the (-)-form produced no change. Both isomer-induced increases in ACh in the accumbens were prevented when 5-HT synthesis was blocked by p-chlorophenylalanine, thus denoting 5-hydroxytryptaminergic mediation of these effects. In striatum, the increase in ACh induced by (+)-fenfluramine was summated with the increase in ACh induced by dopamine receptor stimulation with apomorphine and was not prevented by dopamine receptor blockade with pimozide. On the other hand, apomorphine's effect was blocked by (-)-fenfluramine while pimozide pretreatment unmasked an increase in ACh induced by (-)-fenfluramine. The results favour the notion that there is a population of cholinergic neurons intrinsic to the striatum which is under inhibitory 5-HT regulation and independent of inhibitory dopamine regulation.
In vitro and in vivo α-blocking activity of thymoxamine and its two metabolites
Authors: Creuzet M H , Prat G , Malek A , Fauran F , Roquebert J 
Published: April 2011

Abstract
The α-adrenoceptor potency of thymoxamine and its two metabolites deacetylthymoxamine and demethyldeacetylthymoxamine were determined on the contraction of rat vas deferens induced by noradrenaline, the blood pressure increase induced by noradrenaline given i.v. to dogs and the contraction of the nictitating membrane induced by electrical stimulation in cats. In vivo the three drugs were administered at 6·35 times 10−6 mol kg−1 intravenously. Deacetylthymoxamine presented nearly the same α-blocking activity as the parent drug. This was ascribed in vivo to the rapid deacetylation of thymoxamine. Demethyldeacetylthymoxamine was less active. In vitro its pA2 was 6·20 ± 0·09 compared with 6·75 ± 0·20 for thymoxamine and 6·57 ±0·13 for deacetylthymoxamine. In vivo, it was inactive in dog and less active than the other two drugs soon after its administration in the cat. The oral LD 50 values in the mouse for the three drugs were respectively 0·81, 0·71 and 1·14 mmol kg−1 for thymoxamine, deacetylthymoxamine and demethyldeacetylthymoxamine.
The availability of nitroglycerin from parenteral solutions
Authors: Roberts M S , Cossum P A , Galbraith A J , Boyd G W 
Published: April 2011

Abstract
The availability of nitroglycerin from solutions infused from Viaflex plastic infusion bags or glass infusion bottles through Buretrol plastic giving sets has been examined. Each of the individual components of the infusion bag/giving set system (i.e. infusion bag, burette and infusion tubing) sorbed nitroglycerin to a significant extent. It was found that the extent and rate of nitroglycerin disappearance from solutions stored in each of the components were in the rank order: tubing &gt; burette &gt; infusion bag. The disappearance kinetics of nitroglycerin from solutions stored in each component was more accurately described by a ‘diffusion’ model than by the ‘two compartment kinetic’ model reported previously. The dimensions of the components and the volume of solution used were determinants of the rate and extent of nitroglycerin disappearance. In simulated infusions of nitroglycerin through plastic infusion bag (or glass bottle)/giving set system the flow rate of solution through the plastic infusion tubing affected the concentration of nitroglycerin in the effluent and the extent of sorption by the components of the infusion delivery system. The loss of nitroglycerin in these studies could be accounted for solely by the sorption of nitroglycerin by the plastic components of the infusion bag/giving set system.
The effects of sodium nitroprusside and cyanide on haemoglobin function
Authors: Vesey C J , Krapez J R , Cole P V 
Published: April 2011

Abstract
Incubation of human blood with 0·3 mM sodium nitroprusside (SNP) or 1 mM potassium cyanide (KCN) for 180 min produced a 600-fold increase in red cell cyanide concentration, a 4% decrease in oxygen capacity and a 6% increase in oxygen affinity. These effects were not reproduced in patients receiving SNP by infusion probably because in the clinical situation much smaller amounts of the drug were used and red cell cyanide levels were lower. The in vitro observations could be explained by cyanide either combining directly with the haemoglobin or encouraging its spontaneous oxidation to methaemoglobin during the incubation. Differences in distribution of cyanide between red cell and plasma following incubation with SNP or KCN and the initial lag phase in accumulation of cyanide in the red cell with SNP provide further evidence that nitroprusside breaks down principally within the red cell.
p-Methoxyamphetamine, a potent reversible inhibitor of type-A monoamine oxidase in vitro and in vivo
Authors: Green A L , Hait Mayyada A S El 
Published: April 2011

Abstract
p-Methoxyamphetamine is over 20 times as potent as (+)-amphetamine as an inhibitor of 5-HT oxidation by monoamine oxidase in mouse brain in vitro, with a Ki value of 0·22 μM. It is highly selective towards A-type monoamine oxidase and possesses only weak activity against the B-type enzyme (Ki value about 500 μM with benzylamine as substrate and solubilized rat liver mitochondria as enzyme source). It is 10 times more active than (+)-amphetamine in protecting mouse brain monoamine oxidase from inhibition by phenelzine in vivo. o-Methoxy- and m-methoxyamphetamines inhibit monoamine oxidase both in vitro and in vivo with potencies comparable with, or less than that of (+)-amphetamine.
The distribution and fate of 131 I-labelled liposomes
Authors: Hardy J G , Kellaway I W , Rogers J , Wilson C G 
Published: April 2011

Abstract
The distribution of 131 I-labelled liposomes with sodium iodide entrapped in the aqueous core has been compared with that of a preparation containing iodinated phospholipid, following i.v. administration to rabbits. Liver uptake was observed initially with both liposomes, but the distribution of the former preparation soon became indistinguishable from that of [131 I] sodium iodide. Iodine-131 was still detectable in the liver 150 h after administration of the phospholipid labelled material. Scintigrams showing the distributions of the radionuclides following administration of 131 I-labelled liposomes and 99m Tc-DTPA liposomes indicate that there may be some biliary clearance.
Rectal absorption of insulin suppositories in rabbits
Authors: Ichikawa Kunihide , Ata Isao Oh , Mitomi Mitsuo , Kawamura Shigeo , Maeno Hiroo , Kawata Hiroitsu 
Published: April 2011

Abstract
When insulin solutions (100 U kg−1) at various pH values were placed in the rectum of rabbits, a large decrease in blood glucose concentration was observed except at the pH close to the iso-electric point of insulin. The effect of surface-active agents on the rectal absorption of insulin was examined by measuring the blood glucose concentration after the administration of 2 or 5 U kg−1. Non-ionic ether type, anionic, cationic and amphoteric surfactants as well as bile acids increased the absorption. The optimal effect with suppositories was reached with the addition of 1% polyoxyethylene (9) lauryl alcohol ether. Insulin suppositories containing agents enhancing rectal absorption were compared with the insulin for intravenous, intramuscular and subcutaneous injection. The changes of blood glucose and plasma immuno-reactive insulin concentration after rectal administration of insulin were similar to those after intravenous injection.
Effect of anthraquinone derivatives on canine and rat intestinal motility
Authors: Garcia-Villar R , Leng-Peschlow Elke , Ruckebusch Y 
Published: April 2011

Abstract
The effects on gastrointestinal motility of 3 senna preparations containing 18% oxidized Ca-sennosides, 60% Ca-sennosides, or pure sennosides A + B were tested in dogs and rats as measured by electromyography. Oral administration of the oxidized products in the fasted animal increased the activity of the small intestine within 2 h and reduced both caecal and colonic contractions for 24 h. Severe diarrhoea was present 4–6 h after administration and lasted for at least 1 day. Ca-sennosides had a similar, but weaker effect while pure sennosides affected motility only 6–10 h after oral administration. The intracolonic administration of the oxidized products resulted in an immediate reduction of colon motility for 7–8 h and diarrhoea was present within 40 min. Intracolonic Ca-sennosides and sennosides A + B induced only small changes in the intestinal motility, but diarrhoea also appeared. The results confirm that pure sennosides act predominantly on large intestine motility after their degradation by colonic microorganisms. Oxidized products are already effective in the upper gastrointestinal tract. The early action of Ca-sennosides requires further investigation. Side effects after oral senna treatment such as griping or nausea may be caused by motility changes induced by the presence of small amounts of oxidized products in the drug.
Plasma concentrations of alphaxalone by gas chromatography: comparison with other gas chromatographic methods and gas chromatography-mass spectrometry
Authors: Sear J W , Holly J M P , Trafford D J H , Makin H L J 
Published: April 2011

Abstract
Existing methods for the measurement of plasma or tissue alphaxalone concentrations by gas chromatography are not wholly satisfactory because of the problems of interfering peaks and detector contamination by the silylation reagent. This paper describes an alternative gas chromatographic method using the nitrogen selective alkali flame ionization detector. Plasma samples from patients given Althesin (alphaxalone-alphadolone acetate) were extracted with light petroleum. O-Methyl oximes were formed using methoxyamine hydrochloride, and the O-methyloxime-3-acetate prepared by heating the extract with acetic anhydride-pyridine. Gas liquid chromatography was carried out on a column of 3% OV 17 on Celite 545 (mesh 80–100), initial temperature 235 °C and increasing by 1 °C min−1. Comparison has been made of the O-methyl oxime acetates with trimethylsilyl ethers using both gas chromatography and gas chromatography-mass spectrometry. The results of the two methods were not significantly different. The coefficient of variation for the O-methyloxime-3-acetates at a plasma concentration of 1·09 μl−1 was 6·9%. This method has an improved sensitivity and selectivity over the existing method, and allows determination of the plasma alphaxalone concentrations found in patients receiving Althesin-supplemented anaesthesia.
The application of differential pulse voltammetry at the glassy carbon electrode to multivitamin analysis
Authors: Ballantine J , Woolfson A D 
Published: April 2011

Abstract
Differential pulse voltammetry at the glassy carbon electrode has been applied to the determination of ascorbic acid, pyridoxine and folic acid in a multivitamin preparation. The individual vitamins all gave well-defined peaks in the anodic region with a linear response of peak current to concentration. The water-soluble vitamins were extracted into aqueous solution and folic acid into dibasic potassium phosphate solution. Before determination of pyridoxine, the ascorbic acid peak was depressed by reaction with formaldehyde. Iron (II) present in the multivitamin preparation did not interfere with the analysis. The voltammetric method compared favourably in terms of accuracy and precision with official methods: it was found to be much simpler, with sample manipulation kept to a minimum. The method was found to be generally applicable to the determination of the vitamins in several multivitamin preparations, or, in simplified form, to the determination of the individual vitamin preparations.
Effects of structural variations of non-ionic surfactants on micellar properties and solubilization: surfactants based on erucyl and behenyl (C22) alcohols
Authors: Arnarson Thórdis , Elworthy P H 
Published: April 2011

Abstract
Studies on erucyl alcohol ethoxylated with 24 units and on behenyl alcohol ethoxylated with 21 ethylene oxide units gave values of 10·2 times 103 and 25·4 times 103 for the micellar weights, 74 and 203 for the aggregation number, and 134 and 106 moles water mole−1 surfactant for the micellar hydration, respectively. The solubilization of azobenzene, cortisone acetate, griseofulvin, sulphadiazine, phenylbutazone, betamethasone, tolbutamide, and menaphthone was studied in 2% solutions of the above surfactants, and in cetomacrogol. Excluding sulphadiazine, a linear relationship was found between moles solubilized/mole surfactant, and (log P)/molar volume of solubilizate.
The filling of molten and thixotropic formulations into hard gelatin capsules
Authors: Walker S E , Ganley J A , Bedford K , Eaves T 
Published: April 2011

Abstract
Problems in the formulation and manufacture of conventional solid dose form products include the variation of fill weight and drug content, dissolution control of poorly water soluble drugs and dust generated during manufacture giving rise to cross contamination. We have examined the application of a liquid filling technique for the manufacture of hard gelatin capsules as a means of overcoming some of these. Filling materials are based on water-soluble hot melt polymers such as polyethylene glycol or water-dispersible thixotropic systems of pharmaceutical oils with thixotropic additives. A Zanasi LZ64 capsule filling machine was adapted to fill liquids using a liquid filling pump. No dust is generated during filling and 20 μg doses of drug can be accurately filled without extensive processing. The formulations are simple and do not require specialist ingredients such as lubricants, binders, disintegrants and flow aids. The method of manufacture is reduced to a simple mixing and direct filling operation. The system may be applied to promote the dissolution of poorly water soluble drugs using solid solutions or solid dispersions. Slow release formulations are also available using suitable retard excipients.
The use of liposomes as a model for drug absorption: β-lactam antibiotics
Authors: Kimura Toshikiro , Yoshikawa Michiyo , Yasuhara Masato , Sezaki Hitoshi 
Published: April 2011

Abstract
Liposomes were prepared from egg phosphatidylcholine-cholesterol-diacetylphosphate (80: 20: 5) and total lipid extracts of rat intestinal mucosa, and the permeability of the liposomal membrane to eight β-lactam antibiotics was studied by using a dynamic dialysis method. Although all the antibiotics used here are ionized and poorly lipid-soluble at pH 6·5, some of them are orally active and efficiently absorbed from the small intestine. The release rate constants from the aqueous dispersion of drug-entrapped liposomes were approximately in the order of their absorbability. Intestinal lipid liposomes were more permeable to the antibiotics than egg lecithin liposomes and the release rate constants for the drugs from intestinal lipid liposomes were strongly correlative with their absorption rate constants, except for cephalothin and ampicillin, the deviations of which could be explained by their surface activity. It is suggested that lipid components of the intestinal mucosa and the bilayer structure may play an important role in the absorption process of the antibiotics. The validity of liposomes as a model for the intestinal absorption of drugs is also discussed.
Long-term controlled delivery of levonorgestrel in rats by means of small biodegradable cylinders
Authors: Wise Donald L , Rosenkrantz Harris , Gregory John B , Esber Henry J 
Published: April 2011

Abstract
Hormone release rates from biodegradable cylindrical implants consisting of a physical matrix of [14 C]levonorgestrel and copolymers of [3 H]lactic and glycolic acids have been monitored in rats. Two copolymers were evaluated: one consisted of 90 parts L-lactide/10 parts glycolide (90L/10G) containing 33 or 50% hormone by weight, and the other of 50 parts DL-lactide/50 parts L-lactide (50DL/50L) containing 50% hormone. For each system, 4–6 rods (0·8 times 16 mm) providing 19 mg of steroid per rat were subcutaneously implanted into the scapular regions of 5 rats, and 14 C and 3 H in faeces and urine were determined weekly for 90–724 days. An initial burst of hormone release, peaking at approximately 90 μg day−1, occurred in the first two weeks. This was followed by an approximately zeroorder release for 14 C from all systems. Longer-term release rates were approximately 10–30 μg day−1 for the 90L/10G system containing 33% hormone, a more uniform rate of approximately 25 μg day−1 for the 50DL/50L system and the highest rate of approximately 40 μg day−1 for the 90L/10G system containing 50% hormone. 3 H and 14 C in residual implants of 90L/10G with 33% hormone removed from animals dying of natural causes during the test were assayed. For this system 3 H activity decreased by over 50% within 250 days, compared with &lt; 25 % loss in 14 C activity. The amounts of 3 H and 14 C released were similar over much of the subsequent test period. At the end of the test both polymer and drug were essentially depleted. All animals with the 50DL/50L system died late in the test period. Between days 609 and 724 from 13·7-27·2% initial 14 C and from 10·0-22·1 % initial 3 H was measured in recovered rods. Microscopic inspection of recovered rods showed a loss of core material and tissue encapsulation. There were no signs of local tissue irritation or systemic toxicity.
Comparison of the effect of phenylbutazone, desonide and cyclophosphamide on four types of experimental pleurisy
Authors: Tarayre J P , Lauressergues H 
Published: April 2011

Abstract
The action of phenylbutazone, a non-steroid anti-inflammatory drug, desonide, a corticosteroid, and cyclophosphamide, an immunosuppressant agent, was studied on four types of experimental pleurisy: carrageenan-pleurisy in rats; passive reversed Arthus pleurisy in rats; Bordetella pertussis- delayed hypersensitivity pleurisy in rats and PPD (purified protein derivative)—delayed hypersensitivity pleurisy in guinea-pigs. For each compound, the action on the exudate and on the number of the different categories of leucocytes in the inflammation focus was evaluated. In carrageenan-inflammation, phenylbutazone reduced the oedema and the number of neutrophils and macrophages. Its favourable effect on exudative events in Arthus—and B. pertussis—reactions was not accompanied by high modifications at the cellular level. With the exception of PPD-pleurisy, desonide reduced the three other reactions. Its action related to the exudate and the various leucocyte types, except in the Arthus reaction in which only the number of neutrophils was decreased. The effect of cyclophosphamide was mainly in B. pertussis pleurisy in which it resulted in a decrease of oedema and a reduction in the number of mononuclears. For each compound, correlations between the effect on exudative and cellular phenomena are discussed.