bluuebunny/crossref_metadata_2025 huggingface dataset:
Measurement of dissolution rates of potassium chloride from various slow release potassium chloride tablets using a specific ion electrode
Authors: Thomas W H
Published: April 2011

The in vitro rates of release of potassium ions from slow-release potassium chloride tablets from 12 sources have been compared. Dissolution rates were determined using a modified non-sink method and a modified sink method. Medicament release in both methods was continuously monitored using a potassium ion specific electrode. The release rate constants were derived and the applicability of the Noyes-Whitney equation, Hixson and Crowell's cube root law and Higuchi's equation was studied.
The adrenoceptors mediating catecholamine effects in frog isolated skin
Authors: Ambalavanar Sivakamy , Foster R W , Schnieden H
Published: April 2011

The short circuit current (s.c.c), potential difference (p.d.) and resistance of the frog skin have been studied. Sympathomimetics increased the s.c.c. in order of relative potency: isoprenaline > salbutamol > noradrenaline. The sympathomimetic-induced increase in s.c.c. was antagonized by propranolol and not by phentolamine. A large concentration of practolol was needed to antagonize the isoprenaline-induced increase in s.c.c. The antidiuretic hormone (ADH)-induced increase in s.c.c. was unaffected by propranolol, practolol or phentolamine. The results suggest that the sympathomimetic-induced increase in s.c.c. is mediated by β2-adrenoceptors.
Relaxation of intestinal smooth muscle and calcium movements
Authors: Tomiyama A , Takayanagi I , Takagi K
Published: April 2011

The effects of papaverine, isoprenaline and N6,2′-O-dibutyryl 3′,5′-cyclic adenosine monophosphate (DiBu.C-AMP) on calcium movements in the taenia from the guinea-pig caecum have been investigated and compared with the effects of phenylephrine. Papaverine and DiBu.C-AMP antagonized the contraction of KCl-depolarized muscle induced by CaCl2 and increased 45Ca-efflux from the taenia. Papaverine also significantly depressed 45Ca-uptake by this preparation. These findings suggest that papaverine impairs the availability of calcium to the contractile system and that there may be a correlation between relaxation and increase of 45Ca-efflux. The action of DiBu.C-AMP resembles that of papaverine but its potency is less.
Plasma protein binding of 7-hydroxy-Δ1-tetrahydrocannabinol: an active Δ1-tetrahydrocannabinol metabolite
Authors: Widman M , Nilsson I M , Nilsson J L G , Agurell S , Borg H , Granstrand B
Published: April 2011

7-Hydroxy-Δ1-tetrahydrocannabinol, which is a pharmacologically and psychologically active metabolite of Δ1-tetrahydrocannabinol in man, has been shown by equilibrium dialysis and ultrafiltration to be bound 94–99% to plasma proteins. Further experiments, using the [14C]labelled compound, with agarose and Polyacrylamide gel electrophoresis and ultracentrifugation suggest that albumin, α1-lipoprotein and, to a minor degree, also β-lipoprotein are involved in the protein binding of 7-hydroxy-Δ1-tetrahydrocannabinol in blood plasma.
The effects of changes in ionic environment and modification of adrenergic function on the vascular responses to sympathomimetic amines
Authors: George A J , Leach G D H
Published: April 2011

The responses to each of four sympathomimetic amines: noradrenaline 200 ng, octopamine 50 μg, metaraminol 20 μg and tyramine 100 μg were studied in the perfused rat mesentery preparation. Perfusion with Ca2+- and Mg2+-free solutions potentiated the responses to all four amines compared with control responses obtained during normal Krebs perfusion. Under perfusion conditions using either normal or Ca2+- and Mg2+-free Krebs solution, nialamide and reserpine retained their characteristic effects on the responses to each amine. Cocaine and desipramine abolished the responses to tyramine but potentiated those to noradrenaline and metaraminol under all perfusion conditions. The responses to each of the amines were only antagonized by ouabain when Ca2+ ions were present in the perfusion solution. It is concluded that perfusion with Ca2+- and Mg2+-free solution interferes with the normal uptake mechanisms occurring in the adrenergic neuron.
The effect of corticosterone on extraneuronal amine uptake and effector response in rat salivary glands
Authors: Almgren Olle , Jonason Jan
Published: April 2011

The effect of corticosterone on effector cell response to noradrenaline in vivo and on extraneuronal amine uptake in vitro has been investigated in rat submaxillary glands. When tissue slices were incubated with [3H]noradrenaline the level of extraneuronally retained radioactive material was found to be markedly reduced at a concentration of 10 μg ml−1 of corticosterone after inhibition of neuronal uptake by protriptyline. Corticosterone in a dose of 10 mg kg−1 was found to markedly potentiate the secretory response to noradrenaline in vivo, when the neuronal uptake of noradrenaline was blocked by protriptyline (10 mg kg−1, i.p.). Inhibition of neuronal uptake alone by protriptyline or of the extraneuronal uptake alone by corticosterone in the doses used here did not affect the dose-response curve for noradrenaline, at least not in its lower part. The data thus clearly show that the extraneuronal amine uptake of rat salivary glands is blocked by corticosterone and that this extraneuronal uptake might be regarded as a mechanism of importance for the inactivation of the adrenergic transmitter.
Spectrophotofluorometric and gas-liquid chromatographic methods for the estimation of mexiletine (Kö 1173) in plasma and urine
Authors: Kelly J G , Nimmo J , Rae R , Shanks R G , Prescott L F
Published: April 2011

Methods are presented for the spectrophotofluorometric and gas-liquid chromatographic determination in plasma and urine of the anti-arrhythmic compound, mexiletine (Kö 1173). Both methods involve extraction of the drug from alkaline plasma with ether. In the spectrophotofluorometric method the compound is re-extracted into 0ṁ05n HCl and emission intensity determined at 300 nm with activation at 228 nm. In the chromatographic method the drug is acylated during evaporation of the ether. Both butyryl and acetyl derivatives could be used. Use of a nitrogen-sensitive detector increased the sensitivity and selectivity of the method and allowed more rapid analyses. There was good agreement between results obtained by spectrophotofluorometric and chromatographic methods.
Uptake of [3H]5-hydroxytryptamine and [3H]noradrenaline by slices of rat brain incubated in plasma from patients treated with chlorimipramine, imipramine or amitriptyline
Authors: Tuck J R , Punell G
Published: April 2011

Great interest has been focused in recent years on the purported role of monoamines in the depressive syndrome (for review see McClure, 1971). Monoamine systems in the brains of various species have been mapped out (Fuxe, 1965; Ungerstedt, 1971) and noradrenaline nerve terminals have been demonstrated in human cerebral cortex (Nyström, Olsson & Ungerstedt, 1972). Tricyclic antidepressants have been shown to be effective in about 60% of depressions treated (Bennet, 1967). These drugs affect the monoamine neuron by inhibiting the uptake of the released transmitters noradrenaline and/or 5-hydroxytryptamine (5-HT) through the membrane pump of the nerve terminals. Various tricyclic antidepressants have different profiles of potency in inhibiting the uptake into noradrenaline and 5-HT nerve terminals, each drug having its own pattern (Carlsson, Corrodi & others, 1969; Shaskan & Snyder, 1970; Lidbrink, Jonsson & Fuxe, 1971; Ross, Renyi & Ögren, 1972). We have previously studied the active uptake of [3H]noradrenaIine (3H-NA) and [3H]5-hydroxytryptamine (3H-5-HT) into their respective nerve terminals by using slices of rat cerebral cortex incubated in human plasma which was drawn from patients before and during treatment with antidepressant drugs (Hamberger & Tuck, 1973).
The interaction of penicillins with phospholipids
Authors: Padfield John M , Kellaway I W
Published: April 2011

The interaction of the antibiotics, penicillin G and ampicillin, with sonicated sols of phosphatidylcholine, lysophosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol and phosphatidylserine has been examined by Sephadex gel nitration and dynamic dialysis. Nuclear magnetic resonance spectroscopy provided evidence of a predominantly hydrophobic interaction between the antibiotics and the phospholipids, phosphatidylserine and phosphatidylcholine. Confirmation of hydrophobic interaction was provided by a rheological investigation of the effects of urea and guanidine hydrochloride on the antibiotic-phospholipid complex. Penicillin G was found to interact to a greater degree than ampicillin, a result which is of interest in the light of present knowledge of in vivo activity of these antibiotics.
The activity of β-adrenoceptor blocking agents in protecting mice from the cardiotoxic effects of ouabain
Authors: Lavender Marjorie K , Parkes M W
Published: April 2011

A method is described for the assessment of the protective activity of drugs against the lethal effect of intravenously infused ouabain in mice. Electrocardiographic studies confirmed that protection is exerted against a cardiotoxic action of the glycoside. Activities are quoted for some β-adrenoceptor blocking agents. Both (-)- and (+)-enantiomers of propranolol were active but only the (-)-enantiomer of sotalol and INPEA-drugs devoid of membrane-stabilizing properties.
Behavioural and biochemical interaction between caffeine and l-dopa
Authors: Stromberg Ulf , Waldeck Bertil
Published: April 2011

The modification by caffeine of the effects of different doses of l-dopa on locomotor activity and catecholamine levels in brain was investigated in mice. Caffeine, which in the dose used caused moderate locomotor stimulation by itself, did not alter the depressant effect on motility of medium doses of l-dopa. The hyperkinetic effect of higher doses of l-dopa was, however, potentiated by caffeine. Biochemically the increase in dopamine levels seen after a dose of l-dopa was enhanced by caffeine. It is suggested that at least part of the potentiating effect of caffeine on the l-dopa induced hypermotility is related to the increased cerebral levels of dopamine.
Papaver bracteatum Lindl.—a new plant source of opiates
Authors: Fairbairn J W , Hakim F
Published: April 2011

Certain strains of P. bracteatum Lindl. are reported to contain in the roots significant quantities of thebaine, which can be used for the production of codeine and other opiates. Results from plants raised from Iranian seeds and grown near London for 4 to 5 years are presented. The botanical and chemical characters correspond closely to those of the active strain Halle III described by Böhm (1970) and enable this plant to be clearly distinguished from the closely related P. orientale L. The thebaine content of the roots was 0.25 % which is much lower than the value of 0.7 to 1.3% reported in Halle III roots. The fruiting tops, however, were also investigated and found to contain significant amounts of thebaine in field conditions. If tops were harvested in the summer and roots in the autumn, about 15 kg thebaine per hectare should be produced from our strain grown in the conditions described. This compares favourably with about 1 kg alkaloids per hectare from Turkish opium production or even the 3 kg per hectare from the high yielding Indian farms.
Intestinal absorption, intestinal distribution, and excretion of [14C] labelled hyoscine N-butyl bromide (butylscopolamine) in the rat
Authors: Pentikäinen P , Penttilä Aneri , Vapaatalo H , Hackman R
Published: April 2011

Butylscopolamine was labelled with 14C and its gastrointestinal absorption, biliary and urinary excretion, enterohepatic circulation and gastrointestinal distribution were examined in anaesthetized rats. Biliary excretion was the main elimination route of intra-portally administered [14C]butylscopolamine, with 42% of the dose recovered in the bile during 12 h. About 6% of the radioactivity administered orally as [14C]butylscopolamine was excreted in the bile and 1.2 % in the urine during 24 h, which indicates poor gastrointestinal absorption of butylscopolamine in the rat. When collected radioactive bile was readministered intrajejunally, only about 7% of the radioactivity was recovered in bile and urine during 12 h, which suggests that only a small fraction of butylscopolamine and its metabolites engage in an enterohepatic circulation. After oral administration of [14C]butylscopolamine, radioactivity was found to accumulate in the wall of the distal small intestine, and about 20% of the dose was found in this tissue 24 h after drug administration. As a result, local anti-acetylcholine effects of butylscopolamine might be expected.
An examination of acid-base equilibria of 1,4-benzodiazepines by spectrophotometry
Authors: Barrett J , Smyth W Franklin , Davidson I E
Published: April 2011

Changes of ultraviolet absorption spectra with pH in solution were used to determine pKa values for six 1,4-benzodiazepines. Diazepam, chlordiazepoxide and medazepam as a result of protonation of the molecule in acidic solutions, were found to each have one pKa, while two pKa values were observed for oxazepam, nitrazepam and lorazepam, because of protonation in acid and deprotonation of the neutral molecule in alkaline media. The spectra are explained by considering them to be superimposed spectra of the two benzene rings, one mono-substituted and one tri-substituted, within the molecule. Sites of protonation (principally at nitrogen atoms in position 4 in the diazepine ring) and deprotonation (for oxazepam, nitrazepam and lorazepam) are predicted and the differences in the observed pKa values explained.
Metabolic N- and α-C-oxidation of norephedrine by rabbit liver microsomal fractions and synthesis of the metabolic products
Authors: Beckett A H , Jones G R , Al-Sarraj D S
Published: April 2011

The products of metabolism of norephedrine by 10 000 g fractions of rabbit liver microsomes have been shown to be norephedrine hydroxylamine, l-hydroxy-2-oxo-l-phenylpropane oxime, 1-hydroxy-2-oxo-1-phenylpropane, 1,2-dihydroxy-l-phenylpropane (erythro). N-Oxidation was at least as important as α-C-oxidation. The synthesis and properties of the metabolic products are described.
The dissolution of salicylic acid in micellar solutions of polysorbate 20
Authors: Rees Judith A , Collett J H
Published: April 2011

Dissolution rates of salicylic acid in micellar solutions of polysorbate 20 have been determined at pH 1·0 to 4·0 using a pH-stat to maintain the pH. At any one pH, as the concentration of polysorbate 20 was increased up to 12% w/v, the dissolution rate increased, but a further increase up to 20% w/v polysorbate 20 only slightly increased the dissolution rate. At any one concentration of polysorbate 20 the dissolution rate increased linearly as the pH was increased. The dependence of dissolution rate on such parameters as viscosity of the dissolution medium, diffusion layer thickness and diffusion cofficient has been examined.
Application of orthogonal functions to spectropolarimetric analysis of some penicillins
Authors: Wahbi A M , Ebel S
Published: April 2011

The orthogonal function method is extended to correct for interferences in spectropolarimetric analysis. The method has been applied to the determination of some penicillins in presence of the degradation product penicilloic acid. The results obtained suggest that the method can be widely applied for similar problems.
A new colorimetric method for the determination of methyldopa
Authors: Khalil S K Wahba , Salama R B
Published: April 2011

A rapid and convenient method is described for the determination of methyldopa in pharmaceutical preparations. This is based on measuring the intensity of the orange colour, developed on reacting methyldopa with thiosemicarbazide in alkaline medium, at 490 nm. The colour obeys Beer’s law in a concentration range of 2·0-10 μ-g ml−1. Since the catecholic function with free adjacent positions is required for the development of the colour, the method is highly specific.
The induction of ethanol dependence and the ethanol withdrawal syndrome: the effects of pyrazole
Authors: Littleton J M , Griffiths P J , Ortiz A
Published: April 2011

Daily administration of an inhibitor of alcohol dehydrogenase (pyrazole, 1 m mol kg−1, i.p.) appeared to prevent the development of metabolic tolerance to ethanol administered chronically to mice by inhalation, but increased the duration and intensity of the behavioural change associated with ethanol withdrawal, despite the absence of any marked difference in blood or brain ethanol and acetaldehyde concentrations during ethanol administration in the two groups. (Pyrazole-treated mice were exposed to lower concentrations of ethanol.) Changes in brain monoamine concentrations which occur in mice during chronic ethanol administration were not prevented by pyrazole, but differed in time course under these conditions. Repeated administration of pyrazole intraperitoneally caused weight loss and hypothermia in mice, whether or not ethanol was also given. It is concluded that the combination of pyrazole and ethanol is probably not capable of separating primary effects of chronic ethanol administration from secondary (metabolic) effects, and that inhibition of alcohol dehydrogenase is unlikely to be the sole reason for the potentiation of the ethanol withdrawal syndrome by pyrazole.
Metabolism of nealbarbitone
Authors: Gilbert J N T , Millard B J , Powell J W , Whalley W B , Wilkins B J
Published: April 2011

The human metabolism of 5-allyl-5-neopentylbarbituric acid (nealbarbitone, Censedal), taken orally, has been studied. Comparison of the gas chromatography—mass spectra of extracts from urine with the spectra of model compounds showed nealbarbitone diol (III) to be the only urinary metabolite present in significant amount (about 30–40% of dose); the rate of excretion of diol reached a maximum about 36 h after ingestion of a single 300 mg dose. Treatment of nealbarbitone with a model oxidase of the Udenfriend type resulted only in oxidation of the allyl side-chain to the 2-oxopropyl derivative, in low yield.
The choice of paper and thin-layer chromatographic systems for the analysis of basic drugs
Authors: Moffat A C , Clare B
Published: April 2011

Thirty-seven paper and thin-layer chromatographic systems in general use for the analysis of basic drugs have been examined. Their discriminating powers were measured, both individually and when used in combination. The better systems were found to be thin-layer systems of silica gel sprayed with 0·1n NaOH, dried and run using one of the following solvents: (1) chloroform-methanol (90:10), (2) cyclohexane-toluene-diethylamine (75:15:10) and (3) acetone. A thin-layer cellulose system using n-butanol-water-citric acid (87:13: 0–48) was suitable if speed was not a requirement and a reversed phase paper system run with an aqueous buffer solution (pH 4·58) at 95† was the fastest system examined. Any of these five systems could be used in combination since their correlation coefficients were never higher than 0·61.
The effect of particle size and shape on the flow and failure properties of procaine penicillin powders
Authors: Pilpel N , Walton C A
Published: April 2011

A study has been made of the effects of particle size and particle shape on the shear and tensile properties of batches of dried procaine penicillin powders whose particle shapes were varied by crystallization from different solvents. The following correlations have been established between the mechanical parameters of the powders and their particle size and shape. log C/T = 1·706 − 0·213 log (V/S) — 1·36 αs.v.a.; (n − 1) = 1·329 + 0·0083 (V/S) − 0·128 αs.v.a.; tan Δ= 0·812 + 0·0057 (V/S) + 0·025 αs.v.a.; FF = 6·52 + 0·434 (V/S) − 0·528 αs.v.a. The findings are discussed in relation to the design of filling equipment for unit doses of penicillin.
The influence of additives on the in vitro release of drugs from hard gelatin capsules
Authors: Newton J M , Razzo F N
Published: April 2011

A factorially designed experiment has been used to assess the total percentage of drug released from hard gelatin capsules in vitro as a function of (a) the drug—the drugs being nitrofurantoin, nitrofurazone, oxytetracycline dihydrate and tetracycline hydrochloride; (b) the diluent—the diluents being lactose, Primojel and Dry-Flow starch; (c) the quantity of diluent, either 20 or 80%; (d) the presence (at a 1 % level) and absence of magnesium stearate and (e) the presence (at a 1 % level) and absence of sodium lauryl sulphate. Treatment of the results by analysis of variance, in 5,4, 3 and 2 factor combinations, indicates that the influence of a given factor is often dependent on the other factors. These interdependencies take the form of either a variation in the extent of an effect or the reversal of an effect. The influence of drug and level of diluent show interdependencies of the former kind. Hence, whilst the overall average for drug release indicates that the drugs can be ranked in the ascending order: nitrofurantoin < nitrofurazone < oxytetracycline < tetracycline, the interactions predict that the quantitative ratios of 1:1·8:2·7:5·1 for the drugs above will vary when an additive is present and according to the additive. The rank order will, however, remain unchanged. Similarly, the higher level of diluent will usually increase drug release but not by a constant ratio between drugs. A reversal of an effect is shown by the addition of magnesium stearate, which in some instances increases rather than decreases drug release (its more usual effect). The addition of 1 % sodium lauryl sulphate does not provide a major enhancement of drug release, and in certain cases can be detrimental. There is no consistent order of effectiveness of the three diluents, and thus a universal capsule diluent, which will always improve drug release, does not appear to be a possibility.
Neuromuscular actions of edrophonium in the lateral segmental tail muscle of the rat in vivo
Authors: Whittaker R
Published: April 2011

The actions of edrophonium on neuromuscular transmission in vivo have been studied using the lateral segmental tail muscles of the rat. The drug produced an increase in amplitude of the miniature end-plate potentials (m.e.p.p.s) without an effect on their frequency and increased the amplitude of the end-plate potentials (e.p.p.s) without increasing quantal release of transmitter. It is concluded that the anticholinesterase action of this drug in vivo facilitates neuromuscular transmission, which confirms many of the findings from in vitro studies.
Prostaglandins and the anti-inflammatory activities of aspirin and sodium salicylate
Authors: Smith M J H , Ford-Hutchinson A W , Elliott P N C
Published: April 2011

Acetylsalicylic acid (aspirin) and sodium salicylate are equally effective in reducing the swelling in the carrageenan-induced paw test and the accumulation of leucocytes into the inflammatory exudate produced by the subcutaneous implantation of polyvinyl sponges in the rat. Aspirin but not sodium salicylate caused a significant reduction in the potentiation of paw oedema found after the concurrent administration of carrageenan and arachidonic acid. Some implications of these findings are discussed.
The evidence of the release of prostaglandin-like material from rabbit kidney and guinea-pig lung by (–)-trans- Δ9-tetrahydrocannabinol
Authors: Kaymakcalan S , Ercan Z S , Türker R K
Published: April 2011

Injection of (–)-trans-Δ9-tetrahydrocannabinol (THC) through the renal artery caused a decrease in perfusion pressure and an increase in urine produced by the isolated perfused rabbit kidney. Both effects of THC are inhibited by the prior addition of aspirin to the perfusion medium. THC also induced a dose-dependent increase in perfusion pressure on the isolated perfused lung of guinea-pig and the effluent from the lung produced a contraction on the isolated continuously superfused rat stomach fundus strip. These effects are prevented by the pretreatment of the lung with aspirin which inhibits the production of prostaglandins (PG) and SC 19220 which inhibits the pharmacological effects of PG.
The vascular changes after ephedrine tachyphylaxis
Authors: Morishita H , Furukawa T
Published: April 2011

The changes elicited after ephedrine tachyphylaxis in the dog femoral and rabbit aortic strips isolated from the untreated and ephedrine pre-treated animals have been studied. In untreated strips, ephedrine exhibited dose-dependent contractions which were blocked by phenoxybenzamine. These contractile responses to ephedrine were reduced after pre-treatment with ephedrine in vivo. In rabbit aortic strips previously contracted with noradrenaline or KCl, ephedrine induced dose-dependent relaxations at high concentrations, which were not affected by propranolol. These relaxation responses were likewise diminished after ephedrine. Dose-related contractile responses to noradrenaline were potentiated at low concentrations and depressed at high concentrations after ephedrine whereas those to adrenaline were inhibited over the entire agonist range. Responses to KCl were not affected. These reductions in the responses to noradrenaline and adrenaline after treatment with ephedrine in vivo were inhibited by increased calcium2+ concentration. From the results, it can be presumed that the observed changes in vascular responsiveness may be partially involved in the development of ephedrine tachyphylaxis.
An investigation into the deposition of inhalation aerosol particles as a function of air flow rate in a modified ‘Kirk Lung’
Authors: Davies P J , Hanlon G W , Molyneux A J
Published: April 2011

The effect of air flow rate on the deposition of inhalation aerosol particles in a modified ‘Kirk Lung’ has been studied. Two commerical products were used. The amount depositied in the mouthpiece and throat regions decreases with increasing flow rate. The amount in the collector rises to maximum of approximately 50%. This material represents the therapeutically available portion. Such an apparatus would be useful for routine quality control of the size distribution ratios for inhalation aerosol particles.
The in vitro dissolution of phenobarbitone sodium from ethyl cellulose microcapsules
Authors: Jalsenjak I , Nicolaidou Constantia F , Nixon J R
Published: April 2011

Microcapsules of sodium phenobarbitone, with a wall of ethyl cellulose, have been prepared. The size distribution was determined by use of standard sieves and the effect of core: wall ratio noted. Release of the drug into an aqueous medium was studied. The release pattern was found to have similar characteristics to the release of a drug from an insoluble porous matrix.
Factors affecting the binding of tricyclic tranquillizers and antidepressants to human serum albumin
Authors: Sharples D
Published: April 2011

The linear free energy-related model for structure activity relations developed by Hansch & Fujita (1964) has been used to correlate the binding of tricyclic tranquillizers and antidepressants to human serum albumin (HSA) with hydrophobic and electronic parameters. The parameters chosen being the chromatographic parameter (Rm) and the affinity of charge transfer complex formation (kc). The relative importance of these factors has been assessed by linear and multiple linear regression analysis. Results show that the major factor in binding is electronic with only a minor contribution from the hydrophobic parameter.
Effects of phosvitin on the ecg changes induced under hypoxia in the rat
Authors: Caprino L , Falchetti R , Borrelli F
Published: April 2011

The effect of phosvitin (1 g kg−1, i.p.) on ecg changes induced in rats by a reduction of partial oxygen pressure in the respiratory mixture was studied. Phosphocreatine, phosphoserine, ATP and Na2HPO4.2H2O were also administered intraperitoneally for comparison. Phosvitin alone was found to prevent the hypoxia-induced T-wave changes (flattening or disappearance), which were also temporarily aggravated by injection of noradrenaline. As to the metabolic, hypoxia-induced myocardial changes, two hypotheses are discussed: a release of phosvitin phosphate radicals ready for immediate utilization or a drug action mediated via a membrane-bound intrinsic proteinkinase system.
The effect of propranolol on sympathetic nerve stimulation in isolated vasa deferentia
Authors: Hughes I E , Kneen Barbara
Published: April 2011

(±)-Propranolol hydrochloride (0·5 mg kg−1 twice daily, subcutaneously, for 3 days or approximately 2·4 mg kg−1 daily, orally, for 21 days) failed to produce ptosis or to affect responses to transmural stimulation of isolated vasa deferentia removed from treated mice. In guinea-pig isolated vasa deferentia responses to transmural stimulation through parallel electrodes were reduced by propranolol (1 to 20 μg ml−1); blockade was concentration dependent, fast to equilibrium (45 min), easily reversed by washing but not reversed by (+)-amphetamine sulphate (0·2 μg ml−1). At lower concentrations (0·04 and 0·2 μg ml−1), propranolol marginally potentiated responses to transmural stimulation. In contrast, guanethidine (0·2 μg ml−1) produced a slow onset blockade which was completely reversed by (+)-amphetamine. The response to electrical stimulation through concentric ring electrodes was reduced by low concentrations of propranolol but this effect is ascribed to the known local anaesthetic actions of propranolol and no evidence of true adrenergic neuron blockade was found.
Oxytetracycline tablet formulations: the influence of excipients and the method of granulation
Authors: Chalmers A A , Elworthy P H
Published: April 2011

The proportion of microcrystalline cellulose and alginic acid present as excipients in the dry mix for an oxytetracycline dihydrate tablet formulation, prepared by a conventional wet granulation process, has been shown to influence granule formation and properties. Granule size distributions have varied widely due perhaps to variation in binder distribution. Granulating with water was equally satisfactory to granulating with a PVP solution. Slugged granules produced robust tablets, which disintegrated and dissolved rapidly.
Aggregation of antiacetylcholme drugs in aqueous solution: micellar properties of some diphenylmethane derivatives
Authors: Attwood D
Published: April 2011

Light scattering methods have been used to examine the aggregation in aqueous solution of a series of antiacetylcholine drugs based on the diphenylmethane nucleus. The drugs investigated included adiphenine hydrochloride, piperidolate hydrochloride, benztropine mesylate, orphenadrine hydrochloride, chlorphenoxamine hydrochloride, lachesine hydrochloride, poldine methylsulphate, pipenzolate bromide, clidinium bromide, benzilonium bromide and ambutonium bromide. A micellar pattern of association was established for all compounds and critical micellar concentrations and aggregation numbers have been determined.
Anomalies in some properties of powder mixtures
Authors: Varthalis S , Pilpel N
Published: April 2011

Mixtures of lactose and paracetamol and of lactose and oxytetracycline exhibit anomalous properties. The mean particle sizes, tensile strengths and flow properties of the mixtures are not proportionally intermediate between those of the constituents. The results are ascribed to changes that occur in the packing arrangements of the particles. These changes could have practical consequences in monitoring the progress of a mixing operation by measuring apparent particle size and in controlling the properties of granules, capsules and tablets prepared from the mixtures.
Effect of polymer cation content on certain film properties
Authors: OKOR R S
Published: April 2011

Mixing of two acrylate-methacrylate copolymers designated A and B and differing only in cation (quaternary ammonium) content in the ratio 2:1 (A:B) provided a means of varying polymer cation content in resulting films. Film permeability to the permeant urea, increased with increase in cation content; a two phase change characterized by a slow increase at a low cation content level followed by about 13 times more rapid increase at a high cation content level. The point of transition from the slow to the rapid phase was 53 moles cation per mole polymer chain. On average a 2 fold increase in cation content resulted in a 500 fold increase in permeation rate. Increases in film swelling and pore size also accompanied the increase in cation content, but the change in permeability was more positively correlated with the corresponding change in film pore size. Mutual repulsion by charged groups during film formation is suggested as a factor promoting the formation of large pores in the film at high cation content.
Effects of structural variations of non-ionic surfactants on micellar properties and solubilization: variation of oxyethylene content on properties of C22 monoethers
Authors: ARNARSON THORDIS , ELWORTHY P H
Published: April 2011

Studies on erucyl alcohol ethoxylated with 40 and 47 units, and on behenyl alcohol ethoxylated with 33 and 43 units, gave values of 106, 101, 271, and 304 (all × 103) for the micellar weight, 51, 42, 152, and 137 for the aggregation numbers, and 257, 362, 209, and 311 moles water mol−1 surfactant for the micellar hydration, respectively. Measurements of the solubilization of azobenzene, cortisone acetate, griseofulvin, sulphadiazine, phenylbutazone, betamethasone, tolbutamide, and menaphthone showed that the erucyl derivatives were better solubilizers than the behenyl compounds, and that solubilization increased as the polyoxyethylene chain was shortened; this change was more pronounced with the erucyl compounds.
Pathways of decomposition of propylbenzilylcholine mustard in neutral and alkaline solution
Authors: YOUNG J M
Published: April 2011

High-voltage electrophoresis has been used to follow the decomposition of propylbenzilylcholine mustard (PrBCM) in aqueous solution. Dilute solutions of PrBCM in 10 mM phosphate buffer, pH 7.5, or Krebs-Henseleit solution allowed to stand for 1 h at room temperature (22–24 °C) contain mainly the aziridinium ion derivative. At pH 7.5 the concentration of this ion declines slowly, giving rise first to the N-hydroxyethyl derivative and then ultimately, following hydrolysis of the ester bond, to NN-bis(2-hydroxyethyl)propylamine and benzilic acid. In contrast, in 5 mM NaOH the ester bond undergoes rapid hydrolysis, so that the major species present after 15 min at room temperature is the N-hydroxyethylaziridinium ion. This ion then undergoes slow reaction with hydroxyl ion to yield the same final decomposition product, NN-bis(2-hydroxyethyl)propylamine, as is observed at pH 7.5.
Volume of water-filled pores in the ethyl cellulose membrane and the permeability of microcapsules
Authors: VIDMAR VESNA , Jalšenjak I , KONDO T
Published: April 2011

The volume fraction of the water-filled pores in the microcapsule membranes was calculated and the values from 0.55 to 2.5% were obtained. Differential scanning calorimetry of aqueous suspensions of microcapsules showed no structured water present in the ethyl cellulose membranes. The temperature effect on the apparent diffusion coefficient of a drug was investigated and the apparent activation energy of diffusion was calculated.
An investigation of the relationship between particle size and compression during capsule filling with an instrumented mG2 simulator
Authors: JOLLIFFE I G , NEWTON J M
Published: April 2011

An instrumented mG2 capsule filling machine simulator has been employed to study the effects of the amount of compression (compression ratio) on the capsule fill weight uniformity and measured compression and ejection stresses. Four size fractions of lactose were studied (mean particle sizes 15.6, 17.8, 37.5 and 155.2 μm). The range of compression over which satisfactory filling could be achieved was large for fine, cohesive powders but decreased with increasing particle size. The lower limit of filling ability was the ability to retain the powder and the amount of compression needed to achieve retention increased with increasing particle size. The upper limit on compression, was the compaction of the powder which prevented the piston acting to cause retention. Large particle sizes were able to undergo only a small change in volume before compaction occurred whilst fine, cohesive powders were considerably more compressible and hence could be filled satisfactorily at higher compression settings.
Anti-warfarin antibody preparation and its characterization for radioimmunoassay
Authors: SATOH HIROKO , HAYASHI MASAHIKO , SATOH SUSUMU
Published: April 2011

Anti-warfarin antiserum was prepared in rabbits by immunization with a synthesized warfarin antigen, 4′-azo-warfarin human serum albumin, which possesses two enantiomorphic haptenic sites of warfarin on the molecule. The antiserum recognized both R- and S-warfarin to the same degree, 50% cross reactivities of racemic warfarin, respectively. One of the warfarin metabolites, racemic warfarin alcohol, showed 1% cross reactivity, and R- or S-warfarin alcohol have half the reactivity of the racemic alcohol. Rabbit plasma warfarin levels were determined by radioimmunoassay using this antiserum and racemic [14C]warfarin and by fluorometric assay after isolation by thin layer chromatography. After a single administration of warfarin (2 mg kg−1 orally or 500 μg kg−1 i.v.), the plasma levels determined by both assay methods showed a good correlation (r = 0.97, P < 0.001, Y = 1.04–0.09). The results show that the radioimmunoassay can determine total plasma warfarin without interference of plasma metabolite. The applicability and limitation of the radioimmunoassay for pharmacokinetic study are discussed.
Cardiovascular effects in the rat of ketanserin, a novel 5-hydroxytryptamine receptor blocking agent
Authors: PERSSON BENGT , HEDNER THOMAS , HENNING MATTS
Published: April 2011

Following intravenous administration of ketanserin (0.3–10 mg kg−1) to conscious or anaesthetized normotensive and spontaneously hypertensive rats there were dose-dependent blood pressure reductions but no compensatory tachycardia. Intracerebroventricular administration of ketanserin (25–500 μg) had inconsistent and largely insignificant cardiovascular effects. In a dose range where it produces hypotension ketanserin antagonized the pressor responses to adrenaline and noradrenaline as well as to 5-hydroxytryptamine in monoamine depleted and spinalized rats. It is suggested that the hypotensive action of ketanserin in the rat does not involve a central mechanism but a peripheral α-adrenolytic action is implicated.
Demonstration of maximum solubilization in a polyoxyethylene alkyl ether series of non-ionic surfactants
Authors: ELWORTHY P H , PATEL M S
Published: April 2011

The solubilization of azobenzene, menaphthone, cortisone acetate, and griseofulvin was measured in a series of non-ionic surfactants of structure CH3[CH2](m−1) [OCH2CH2]1.25mOH, where m varied from 8 to 18. Maximum solubilization occurs when m = 16 (the hexadecyl alkyl ether). This is explained in terms of changes in the oxyethylene mantle close to the micelle core/mantle interface, which appears to be the main locus of solubilization. Micellar properties of CH3[CH2]17[OCH2CH2]22OH are also reported and discussed.
A study of enzyme and protein microencapsulation—some factors affecting the low apparent enzymic activity yields
Authors: WOOD D A , WHATELEY T L
Published: April 2011

Microencapsulation of aqueous solutions of enzymes, α-chymotrypsin (EC 3.4.21.1) and histidase (EC 4.3.1.3), with semipermeable polyamide membranes resulted in a loss of enzymic activity. The low yields (less than 40%) found with both enzymes were typical of others reported in the literature. The activity of broken histidase-containing microcapsules was greater than that of the microcapsules before breaking, and this was interpreted as being due to a simple diffusional restriction on the substrate and product. The maximum of the apparent pH-activity curve of α-chymotrypsin was found to be shifted one unit to more alkaline pH when the enzyme was encapsulated. This phenomenon was explained in terms of the hydrogen ion concentration in the microenvironment surrounding the enzyme being different from that in the bulk solution. Microencapsulation of aqueous solutions of enzymes is accomplished by in situ polymerization reactions at the interface of a water-in-oil emulsion. 125I-labelled proteins (albumin and fibrinogen) were encapsulated under similar conditions to determine the efficiency of the microencapsulation process. About one third of these proteins was lost during the overall preparation procedure and a further fraction was attached to the membranes of the microcapsules.
Nabumetone (BRL 14777, 4-[6-methoxy-2-naphthyl]-butan-2-one): a new anti-inflammatory agent
Authors: BOYLE E A , FREEMANM P C , MANGAN F R , THOMSON M J
Published: April 2011

Nabumetone is a compound of novel structure which displays acute anti-inflammatory activity in the carrageenan-induced oedema model in rats and the ultraviolet-induced erythema model in guinea-pigs. Its activity in these tests is greater than that of aspirin but less than that of naproxen and indomethacin. In the cotton pellet-induced granuloma model in the rat, the compound is active and produces no signs of toxicity at doses much greater than the lowest effective dose, unlike aspirin, naproxen or indomethacin. Nabumetone is also active in the adjuvant-induced arthritis test in rats. In contrast to aspirin, indomethacin and naproxen, the compound is well tolerated by the stomach of fasted rats at doses in excess of those with anti-inflammatory activity. These findings could be linked to the relatively poor ability of nabumetone to inhibit the synthesis of prostaglandins in vitro and to its non-acidic structure. The compound has greater mild analgesic activity than paracetamol, is equi-active with phenylbutazone, but less active than aspirin, naproxen and indomethacin. Nabumetone also has antipyretic activity in the rabbit. No interactions with the hypothalamic-pituitary-adrenal axis have been found.
The effect of a novel, non-steroidal anti-inflammatory compound, nabumetone (BRL 14777), on cellular infiltration into 24-hour polyvinyl sponge implants in the rat, compared with some steroidal and nonsteroidal anti-inflammatory drugs
Authors: BOYLE ELIZABETH A , MANGAN F R
Published: April 2011

The time-course of cell migration into saline-soaked sponge implants over 5 days showed peak polymorphonuclear leucocyte (PMNL) infiltration at 24 h. In common with the corticosteroids dexamethasone and hydrocortisone, and the non-steroidal anti-inflammatory drugs indomethacin, (+)-naproxen, BW 755C and benoxaprofen, nabumetone decreased cell migration into the sponges. PMNLs and mononuclear cells were reduced at 24 h, and there was a parallel decrease in exudate levels of the lysosomal acid hydrolase β-N-acetyl glucosaminidase [NAG ECB, 3, 2, 1, 30]. Impregnation of sponges with λ-carrageenan (1%) caused a 2–3 fold increase in cell numbers, with a relatively greater proportion of PMNLs; drug effects were more marked in these implants.
Particles in small volume injections
Authors: Taylor S A , Spence J
Published: April 2011

The level of particulate contamination in small volume injections has been examined using the light blockage (HIAC) and electrical sensing zone (Coulter counter) techniques, the HIAC system being found to be the more suitable. Particle counts on the same batch of injection showed a large and variable difference between the HIAC and the Coulter counter results, especially below 5 μm. None of the injections examined complied with the British Pharmacopoeia limits for particulates in large volume parenterals, suggesting the unsuitability of the limits for small volume parenterals.
The effects of BW755C and other anti-inflammatory drugs on eicosanoid concentrations and leukocyte accumulation in experimentally-induced acute inflammation
Authors: Salmon John A , Simmons Paula M , Moncada Salvador
Published: April 2011

BW755C (3-amino-1-[m-trifluoromethyl)phenyl]-2-pyrazoline HCl) reduced the concentration of leukotriene B4 (LTB4), thromboxane B2 (TXB2) and prostaglandin E2 (PGE2) in exudate derived from the subcutaneous implantation in rats of 0˙5% carrageenanimpregnated polyester sponges. Polymorphonuclear leukocyte (PMN) migration into the inflammatory exudate was also decreased. The inhibition of LTB4 may, in part, account for the lower number of cells in the exudate since LTB4 is a potent leukotactic agent. Inhibition of LTB4-formation and cell migration by BW755C was dose-related, but the two dose-response curves were not parallel. Cell influx still occurred at doses of BW755C that completely inhibited formation of LTB4: this indicates that, although LTB4 may have a chemotactic role in-vivo, other factors must also contribute to cell migration into the inflammatory exudate. Treatment of rats with dexamethasone also caused a reduction in leukocytes and eicosanoids in the exudate. As with BW755C, there was a differential effect on PMN and LTB4: dexamethasone (1 mg kg−1) reduced PMN accumulation by 40% but LTB4 formation was inhibited by 70%. Leukocyte accumulation was also inhibited by the non-steroidal anti-inflammatory drugs (NSAID's), indomethacin and flurbiprofen. These drugs reduced the concentration of both PGE2 and TXB2 in exudate but that of LTB4 was unchanged. This suggests that reduction of PMN accumulation by indomethacin and flurbiprofen is mediated by a mechanism other than inhibition of LTB4-synthesis. Aspirin also reduced the levels of PGE2 and TXB2 in the exudate but did not consistently affect PMN influx, thereby confirming that inhibition of cyclo-oxygenase does not reduce cell migration in inflammation.
The effects of polymorphism, particle size and compression pressure on the dissolution rate of phenylbutazone tablets
Authors: Tuladhar M D , Carless J E , Summers M P
Published: April 2011

The dissolution rate of phenylbutazone from tablets after disintegration has been used to determine whether the drug particles underwent crushing or bonding during compression. Two polymorphic forms of the drug were used and the predominant effect for high drug concentration (60%), during compression was dependent upon the original particle size of the drug and its polymorphic form. With a low drug concentration (10%) in the tablet, the diluent protected the drug particles from bonding together. The particle size change of the drug during compression was affected by the nature of the diluent present. Lactose had an abrasive action on Form A phenylbutazone compared with Avicel but had little effect on the more ductile Form B. When the contact time of compression was decreased from 29 to 0·-26 s, the 6 μm particles of drug showed less bonding at the shorter time (faster rate of compression) but the effect observed with the larger particles was independent of the compression rate.
Determinants of systemic availability of promethazine in rabbits
Authors: Taylor G , Houston J B
Published: April 2011

Promethazine blood concentration-time curves have been determined in 7 rabbits following intravenous, oral and hepatic portal vein administration of promethazine. This phenothiazine has a large volume of distribution and a high metabolic clearance resulting in low blood concentrations particularly when the oral route is used. Analysis of the areas under the blood concentration-time curves indicates that hepatic first-pass metabolism is the major determinant of promethazine’s low oral availability. Absorption from the gastrointestinal tract is essentially complete in most rabbits and the contribution of metabolism by the intestinal mucosa is minimal. The present findings are compared with the literature on other phenothiazines.