bluuebunny/crossref_metadata_2025_split huggingface dataset:
Size analysis of metered suspension pressurized aerosols with the Quantimet 720
Authors: Hallworth G W , Hamilton R R 
Published: April 2011

Abstract
A method is described for particle sizing of pressurized metered suspension aerosols by collection in a settling drum followed by microscopic evaluation of the slides with a Quantimet 720 automatic image analyser. The method gives satisfactory representation of the distribution of particles settling to the drum base, and demonstrates the excellent stability and reproducibility between and within aerosol packs for two widely used inhalation products. There is much drug deposition of somewhat finer size distribution on the wall of the drum than on the drum base. In spite of this wall loss, the method gives only slightly higher results for the weight and number mean diameters, than when both wall and base distributions are considered. The Quantimet was found to be suitable for particle sizing salbutamol used in preparing aerosol products.
The granulation of binary mixtures: the effects of the properties of the component powders on granules
Authors: Opakunle W O , Spring M S 
Published: April 2011

Abstract
Sulphanilamide and citric acid individually and in various proportions with lactose, have been granulated by massing and screening. There was an optimum blend, that produced granules of maximum mean size and strength, for each binary system examined. The proportion of the components of this optimal blend was dependent on the physical properties of the second component in a mixture with lactose. Results from three systems, lactose: boric acid, lactose: sulphanilamide and lactose: citric acid indicate that although part dissolution of powder during granulation is a factor affecting granule properties, in some systems other physical properties of the second component may become dominant. It is suggested that the combined effect of cohesiveness and wettability of the powders may make the major contribution to granule strength with the sulphanilamide systems. The ultimate mean granule size produced is determined by the wettability or solubility of the powders, or both, in all cases examined. The great affinity of citric acid for aqueous binder solution was the dominant factor determining the properties of granules prepared from lactose: citric acid mixtures.
Studies with the International Pyrogen Standard on the sensitivity and reproducibility of pharmacopoeial pyrogen testing
Authors: Simon S , Tóth M , Wallerstein Gy , Remény Zs 
Published: April 2011

Abstract
Rabbits, 27 or 36 in each experiment, were injected with the International Pyrogen Standard (I. P. St.) in different seasons. The maximum temperature rises were registered, randomized and interpreted according to the requirements of the B.P. (1973), U.S.P. (1970), P. Hung. (1970) and P. Nord. (1962). Although the dose of 3·5 ng kg−1 I. P. St, proved to be non-pyrogenic as tested in summer, when tested in winter the same dose was qualified pyrogenic (to be rejected) by up to one third of the combinations by the criteria of the four Pharmacopoeias. In the spring experiment “to be rejected” qualifications predominated as based on the response of large groups of rabbits. Exclusion of the rabbits showing low sensitivity (before randomization) barely influenced the results with 3·5 ng kg−1 I. P. St. in the experiment in which the mean temperature rise was 0·49°. If, however, the mean temperature rise was higher (0·57 or 0·69°), such a selection practically resulted in the disappearance of “passable” qualifications in the triplet groups and a great predominance of “to be rejected” qualifications in the larger groups. The dose 7·0 ng kg−1 consistently proved to be pyrogenic in large groups of rabbits.
Use of the mouse jumping test for estimating antagonistic potencies of morphine antagonists
Authors: Cowan Alan 
Published: April 2011

Abstract
The potencies of 19 reference morphine antagonists have been compared in a modified version of the mouse jumping test. Mice were each implanted subcutaneously with one 75 mg pellet of morphine. Antagonist challenge took place 72 h later and the incidence of repetitive vertical-jumping was monitored over 1 h. A high Pearson correlation coefficient (r = 0·997) was found between quantitative assays based on the total number of jumps per mouse and quantal assays based on mice jumping at least 6 times. A comparison of relative potencies obtained with the mouse test and with non-withdrawn morphine-dependent monkeys gave a Spearman rank order coefficient of 0·91 while a similar comparison with values obtained with the guinea-pig isolated ileum preparation also gave a high correlation coefficient (r = 0·92). Whereas it is difficult to assess the antagonistic component of buprenorphine and cyclorphan with the ileum preparation, both compounds can be satisfactorily assayed in the mouse jumping test. The reported antagonistic properties of ketocyclazocine and profadol could not be confirmed in the mouse model.
The narcotic discriminative stimulus complex: relation to analgesic activity
Authors: Colpaert F C , Niemegeers C J E , Janssen P A J 
Published: April 2011

Abstract
The ability of drugs to produce the narcotic discriminative stimulus complex is found to be highly correlated with their analgesic activity; in contrast, no relation with their antidiarrhoeal activity is evident. The findings suggest that the narcotic discriminative stimulus complex is a centrally mediated effect of narcotic drugs.
Acetylcholinesterase and responses to acetylcholine in the embryonic chicken heart
Authors: Lelorier J , Shideman F E 
Published: April 2011

Abstract
Three and 4 day old embryonic chicken hearts were examined for their responsiveness to acetylcholine and presence of acetylcholinesterase (AChE) to determine the role of the enzyme in the cardiac effects of the transmitter. The effects of acetylcholine on rate and contractility of 3 day old hearts were indistinguishable from those on 4 day old hearts. These effects were readily blocked by atropine at both stages of development. In 3 day old hearts the responses to acetylcholine were not affected by the AChE inhibitor physostigmine but in 4 day old hearts they were considerably potentiated. The effect of acetylcholine on the rates of 4 day old hearts is of short duration (5 min or less). In 3 day old hearts it persists for a much longer time. Thus, the appearance of AChE in the embryonic heart of the chicken does not seem to modify the responsiveness of the cholinergic receptor to the transmitter.
Some effects of urea on drug dissolution
Authors: Collett J H , Flood B L 
Published: April 2011

Abstract
Solubilities and dissolution rates of salicylic acid have been determined in urea solutions at different pH values. Solubilities increased with pH and urea concentration; a solubilization mechanism was considered to be operating. The solubilization effect of urea was greatest on the non-ionized moieties of the solute. Dissolution rates of salicylic acid increased with pH and urea concentration. The increase in dissolution rate paralleled increases in solubility. The role of solubilizing effect in the enhancement of dissolution rate by urea is discussed.
Solubilization of hydrocortisone, dexamethasone, testosterone and progesterone by long-chain polyoxyethylene surfactants
Authors: Barry B W , Eini D I D El 
Published: April 2011

Abstract
Solubility and dialysis methods were used to study the solubilization of hydrocortisone, dexamethasone, testosterone and progesterone in aqueous long-chain polyoxyethylene non-ionic surfactant solutions. Partition coefficients, Km, between micellar and aqueous phases were calculated between 10–50°. Km decreased with temperature and polyoxyethylene chain length but increased with decrease in steroid polarity. The standard free energy change, ΔGos, for the solubilization of the steroids decreased with decrease in steroid polarity and surfactant hydrophilic chain length but was essentially independent of temperature. The enthalpies and entropies for the process were determined from the variation of Km with temperature. ΔHos and ΔSos increased with decreasing steroid polarity but were essentially independent of temperature and polyoxyethylene chain length.
Oxytetracycline tablet formulations: the effect of wet mixing time, particle size and batch variation on granule and tablet properties
Authors: Chalmers A A , Elworthy P H 
Published: April 2011

Abstract
The wet mixing time has been shown to influence the properties of an oxytetracycline dihydrate tablet formulation, wet granulated with PVP solution. Increased time of wet mixing produced larger, stronger and more dense granules, which compressed into tablets with longer disintegration and dissolution times. Decreased drug particle size aggravated these trends. A decrease in drug particle size also produced larger, stronger and more dense granules. Above an oxytetracycline mean particle diameter of about 6 μm, the tablet dissolution was satisfactory. As the oxytetracycline particle size was decreased further, however, the distintegration and dissolution of the corresponding tablets was markedly slower.
Fluorimetric assay of tetracycline mixtures
Authors: Hall D 
Published: April 2011

Abstract
A simple and precise fluorimetric method is described for the simultaneous assay in plasma of a mixture containing chlortetracycline, demethylchlortetracycline and tetracycline. Assay within the therapeutic ranges of 0–5 mg litre−1 is achieved by formation of strongly fluorescent aluminium/tetracycline complexes, without prior extraction or separation of the individual antibiotics. This is performed by determinations at the peak excitation and fluorescence emission wavelengths of each tetracycline chelate. The method can be similarly applied to the assay of oxytetracycline, rolitetracycline and minocycline.
Differential effect of neuroleptic drugs on dopamine turnover in the extrapyramidal and limbic system
Authors: Bartholini Giuseppe 
Published: April 2011

Abstract
In gallamine-immobilized cats, the caudate nucleus and the nucleus accumbens septi were perfused by means of a push-pull cannula and dopamine was measured in the perfusate. Chlorpromazine (10 mg kg−1) and clozapine (20 mg kg−1), administered intravenously, enhanced the release of dopamine. The effect of chlorpromazine was similar in both regions whereas that of clozapine was more pronounced in the nucleus accumbens than in the caudate nucleus. Furthermore, in the rat, sulpiride, clozapine and thioridazine increased the homovanillic acid concentration in striatum and limbic system to a similar extent. However, following probenecid administration, the net effect of these drugs on homovanillic acid accumulation was more marked in the limbic system than in the striatum whereas haloperidol and chlorpromazine had a similar effect in the two regions. It is concluded that, in contrast to haloperidol and chlorpromazine, sulpiride, clozapine and thioridazine may preferentially affect the limbic dopaminergic transmission. This possibly accounts for the fact that sulpiride, clozapine and thioridazine display an antipsychotic action and yet cause less extrapyramidal side effects than haloperidol and chlorpromazine.
Effects of α-methyldopa on blood pressure in the anaesthetized dog
Authors: Blower P R , Poyser R H , Robertson M I 
Published: April 2011

Abstract
Intravenous infusion over 1 h of 20 mg kg−1 of α-methyldopa produced hypotension in the anaesthetized dog. The magnitude of this effect was, however, inversely correlated with bodyweight. Either rapid intravenous injection of α-methyldopa or slow infusion of α-methyldopate was less effective in lowering blood pressure than infusion of free α-methyldopa, in dogs of equivalent bodyweight. Infusion of α-methyldopa into a vertebral or internal carotid artery produced hypotensive responses but these were no greater and generally less than those obtained to intravenous infusion. α-Methyldopa was therefore capable of producing hypotension in the dog but no evidence was obtained for this being the result of an action within the brain.
Release kinetics of sparingly soluble drugs from ethyl cellulose-walled microcapsules: theophylline microcapsules
Authors: BENITA S , DONBROW M 
Published: April 2011

Abstract
Release rates of theophylline from ethyl cellulose-coated microcapsules were measured as a function of wall thickness and core particle size. The kinetic data conformed with first order release and also the Higuchi matrix model. However, application of the differential rate treatment, hitherto applied only to drug matrix dispersions, showed that release from the microcapsules definitely followed the first order equation. For the purpose of confirming that the release process was membrane-controlled, the experimental rate constants were transformed into effective permeability constants (P1) with the aid of the microcapsule dimensional parameters needed in the relevant equations and compared with the permeability constant (P) of theophylline measured experimentally using planar ethyl cellulose membranes. P1 values decreased linearly to a moderate extent with wall thickness, probably due to decrease in porosity during wall-formation. P1 values of the thicker-walled microcapsules were found to be of the same order as the membrane P value, supporting a release mechanism of membrane control under non-steady state conditions.
The anticoagulant activity of heparins in dextrose solutions
Authors: ANDERSON W , HARTHILL J E 
Published: April 2011

Abstract
Changes with time in the anti-factor Xa activity of several heparins were determined in freshly autoclaved and unautoclaved dextrose solutions. In the former, activity was raised, in the latter a reversible fall occurred at certain heparin concentrations, and the term ‘dextrose effect’ is applied to the difference in activity in the two types of dextrose solutions. A simple dependence on heparin concentration for the rise in activity in autoclaved dextrose solutions contrasted with a threshold heparin concentration in the unautoclaved dextrose solutions. Above this a fall and below it a rise in activity were demonstrated with one factor Xa method. The pH of the two dextrose solutions differed by one unit but pH was not the principal factor in the effect; salt tended to eliminate the dextrose effect which was found mostly with the high and to some extent also with the low molecular weight fractions of pharmacopoeial heparin. There was no evidence for heparin degradation but activity changes, which differed for different heparins, are thought to be associated with the effects of heparin-dextrose interaction modified in the case of autoclaved dextrose by by-products of autoclaving. Generally, proprietary dextrose solutions gave variable results.
Inhibition of human lymphocyte transformation by two aryloxyalkylamidines
Authors: TRIST D G , WEATHERALL M 
Published: April 2011

Abstract
The incorporation of [3H]thymidine into human lymphocytes stimulated by phytohaemag-glutinin (PHA) was inhibited by anilino-N-2-m-chlorophenoxypropylacetamidine (501C) and xylamidine. These amidines antagonize 5-HT, but 5-HT did not alter [3H]thymidine incorporation. 501C inhibited PHA-induced lymphocyte transformation as observed by [3H]thymidine incorporation, [3H]uridine incorporation, [3H]leucine incorporation, DNA content, potassium content, and histological examination. 501C also inhibited increased [3H]thymidine incorporation in human mixed lymphocyte cultures. The IC50 of 501C for inhibition of these processes lay between 4 and 8 μM. When added late in culture (after 6-8 h) 501C was less effective. Possible mechanisms by which 501C inhibits transformation are discussed.
Plasma protein binding of fentanyl: the effect of hyperlipoproteinaemia and chronic renal failure
Authors: BOWER SUSANNE 
Published: April 2011

Abstract
Hyperlipoproteinaemic patients with raised pre β-, or pre β- and β-lipoprotein fractions snowed a significant (P &lt; 0.001) increase in binding of fentanyl to whole plasma, compared with normal subjects. The presence of chylomicra had no significant effect on binding. In patients with chronic renal failure, a correlation of probability P &lt; 0.07 was found between percent binding and concentrations of pre β-lipoprotein (P = 0.001), serum albumin (P = 0.0101), total protein minus albumin (P = 0.0576) and β-lipoprotein (P = 0.0625). There was no significant correlation of binding with elevation of α- or γ-globulins, with urea or creatinine concentrations, or with age or sex (P ≥ 0.223). The magnitude of changes in the free fraction found in these patients should not produce a clinical effect as the total distribution volume of fentanyl exceeds 200 litres.
Effects of N-aralkyl substitution of β-agonists on α- and β-adrenoceptor subtypes: pharmacological studies and binding assays
Authors: DECKER N , QUENNEDEY M C , ROUOT B , SCHWARTZ J , VELLY J 
Published: April 2011

Abstract
The pharmacological and binding properties of four β-adrenomimetic drugs with N-alkyl substitutions (isoprenaline, terbutaline, salbutamol and soterenol) were compared with those of four corresponding drugs with N-aralkyl substitutions (protokylol, ME 506, salmefamol and zinterol). BD-40 A, a very powerful β2-agonist with a related chemical structure, was also included in this study. The β1- and β2-activities of these drugs were determined on guinea-pig atria and trachea, their α-adrenolytic activity was measured on rat aorta and their affinities (Ki) for α1- and α2-adrenoceptors on rat cortical membranes were assessed using [3H]prazosin and [3H]yohimbine. In this group of β-agonists, substitution of the N-alkyl by an N-aralkyl group had a variable effect on the β2-selectivity whereas α-adrenolytic properties were always enhanced. An increase of the affinities (Ki) for both α1- and α2-adrenoceptors was found but the effect was much more pronounced for α1-adrenoceptors. These results indicated that the α-adrenolytic activity observed with the N-aralkyl β-agonists was selective for α1-adrenoceptors.
Interparticle forces in binary and ternary ordered powder mixes
Authors: STANIFORTH J N , REES J E , LAI F K , HERSEY THE LATE J A 
Published: April 2011

Abstract
An ultracentrifuge technique, previously described by Staniforth et al (1981), has been used to study the adhesion profiles of several binary and ternary ordered powder mixes of pharmaceutical interest. The adhesion profile of an ordered mix provides information about the proportion of drug powder adhering with different forces of attraction to the carrier excipient particle surface. The excipient particle size is shown to affect adhesion between the components of a binary ordered mix-recrystallized lactose formed more stable ordered mixes with drug powder when the carrier particle size was increased. Changes in the adhesion profile of each binary system on adding three different fine-powder excipients to form a ternary ordered mix are also examined. The physical properties of carrier particles and the charge interactions of a third powder component with previously formed binary ordered mixes, are found to influence the physical stability of ternary ordered mixes.
A comparison of log P and molecular connectivity in the structure-activity analysis of some antimicrobial agents
Authors: BOYD J C , MILLERSHIP J S , WOOLFSON A D 
Published: April 2011

Abstract
Several congeneric series of antimicrobial agents previously studied by Hansch analysis have been investigated using molecular connectivity as the descriptor of molecular structure. In all cases connectivity gave comparable or improved correlations compared with log P, particularly where the pattern of molecular substitution was more complex. It was concluded that the use of computer-generated connectivity terms had advantages over calculated log P values in its ease of application and should be considered at least for initial screening of structure-activity data.
Quantitation and urinary pattern of 4,4′-dihydroxyantipyrine, 4-hydroxy-antipyrine and 3-hydroxymethyl-antipyrine, as main metabolites of antipyrine in man and rat
Authors: BÖTTCHER J , BÄSSMANN H , SCHÜPPEL R 
Published: April 2011

Abstract
A t.l.c.-assay has been developed for the simultaneous determination from the urine of man and animals of three major hydroxylated metabolites of antipyrine (4,4′-dihydroxy-antipyrine, 4-hydroxy-antipyrine, 3-hydroxymethyl-antipyrine). The methodology is also applicable to bile fluid, liver perfusate and liver homogenate. Genuine conjugates are cleaved by acid hydrolysis and free, acid stable metabolites are extracted. Extracts are subjected to t.l.c. and the chromatograms analysed quantitatively by u.v.-reflectance measurements using authentic materials as standards. Calibration curves are linear with a correlation coefficient r &gt; 0.990. Recovery for each metabolite is &lt;95%. Reproducibility of the method is good, with variation coefficients in the range of 3–7%, depending on concentration. The sensitivity of the method is sufficient for practical needs. The specificity of the procedure was confirmed using radio-labelled antipyrine. In man, 4-hydroxy-antipyrine is the principal hydroxylation product in this series, accounting for about 35–40% of the dose. 3-Hydroxymethyl-antipyrine makes up for about 13–17% and 4,4′-dihydroxy-antipyrine represents 3–6% of the dose of antipyrine. In the rat, 4-hydroxy-antipyrine accounts for about 15–31%, 3-hydroxymethyl-antipyrine for 22–28% and 4,4′-dihydroxy-antipyrine for up to 11–18% of the dose. Variation of this pattern in different strains is moderate. In both species, the major portion of phase-I-metabolites is excreted as conjugates. Part of them appears in a free form.
Gastrointestinal and hepatic first-pass metabolism of aspirin in rats
Authors: IWAMOTO KIKUO , TAKEI MIYUKI , WATANABE JUN 
Published: April 2011

Abstract
The first-pass effect of aspirin was measured in male Wistar rats by comparing the plasma concentration after intravenous, oral or intraportal administration (10 mg kg−1) of the drug. Approximately 88 and 86% of the dose was excreted mostly as salicylic acid and its conjugated forms, glucuronide and sulphate, in urine within 48 h of i.v. or oral administration, respectively. This suggests that the gastrointestinal absorption of aspirin was essentially complete in rats. On the average, the area under the plasma concentration-time curve for unchanged aspirin following oral dosing (AUCo) was 0.35 of that obtained following i.v. administration (AUCi.v) and 0.53 of that following intraportal administration (AUCp). Therefore, orally administered aspirin is subject to first-pass metabolism both in the gut and in the liver of rats. The gastrointestinal first-pass effect is estimated to be relatively more important than the hepatic effect.
The uptake of fentanyl by erythrocytes
Authors: BOWER SUSANNE 
Published: April 2011

Abstract
Fentanyl passed rapidly into and out of erythrocytes to equilibrate with plasma concentration, and a red cell/plasma partition coefficient of 1.01 ± 0.0083 s.e.m. was found in 15 normal subjects. Most of the binding of fentanyl by red cells was by haemoglobin. 10% was bound by the cell membrane. Partition was unaffected by haematocrit, pH, or the concentration of fentanyl up to 0.5 mg ml−1 of blood. Dilution of plasma proteins, and replacement of plasma by buffer showed that uptake of fentanyl by red cells is a linear function of the concentration of free drug in plasma. A partition coefficient for red cells/buffer of 4.91 ± 0.032 s.e.m. was found. This relation was confirmed where binding to plasma proteins was altered in uraemia or hyperlipoproteinaemia, or by competitive displacement of fentanyl by aspirin and phenylbutazone thereby changing the size of the free fraction of fentanyl in plasma. Quinidine, however, inhibited the binding of fentanyl to plasma proteins and red cells equally, to maintain a partition coefficient of unity.