bluuebunny/crossref_metadata_2025_split huggingface dataset:
Placebo granules as cores for timed release drug delivery systems
Authors: Friedman M , Donbrow M , Samuelov Y 
Published: April 2011

Abstract
A drug delivery system is proposed constituted of spherical placebo granules as cores with polymeric surface films containing drug. This timed release dosage form has been prepared by means of a fluidized bed coating technique using ethyl cellulose as the polymeric film and caffeine and salicylic acid as model drugs. The release of the drugs from the dosage form (a) at different drug concentrations and (b) into solutions of different pH showed that drug release was linearly related to the square root of time. Good agreement was found between the theoretical release rate of caffeine, calculated according to Higuchi's equation for a homogenous matrix using membrane permeation parameters measured on linear films, and the experimental results in the case of low drug concentrations. Deviation of the release rate from the homogenous model at high drug concentrations could be explained by crystallization of the drug from the film.
The stability of betamethasone-17-valerate in semi-solid bases
Authors: Yip Y W , Po A Li Wan 
Published: April 2011

Abstract
The stability of betamethasone-17-valerate in semi-solid bases has been investigated. Emphasis has been placed on the stability problems which could arise upon dilution of proprietary preparations by the use of model systems. Betamethasone-17-valerate has been shown to decompose to betamethasone-21-valerate and betamethasone alcohol. Quantitation of the decomposition was by direct densitometry on thin layer chromatographic plates. The decomposition was found to be an apparent first order process and to depend on the diluent used and its concentration. Attempts were also made to relate the rate of decomposition to the pH of the base used, and to stabilize the products.
The determination of aluminium in antacid formulations by Gran's Plot titration with sodium fluoride
Authors: Cooper M E A , Ballantine J , Woolfson A D 
Published: April 2011

Abstract
The aluminium content of a number of proprietary antacid formulations has been determined by titration with sodium fluoride, using the fluoride activity electrode as an end-point detector. Results compared favourably with the official method. The fluoride titration, however, involved less sample manipulation and was more rapid to carry out. End-point detection was made easier by treating titration data by the Gran's Plot method.
The influence of binder concentration on the bond formation of pharmaceutical granules
Authors: Stanley-Wood N G , Shubair M S 
Published: April 2011

Abstract
The formation of particle mucilage bonds with dicalcium phosphate dihydrate and starch mucilage binder reduces the B.E.T. nitrogen adsorption surface area from 1.6 to 0.96 m2 g−1. The maximum reduction (40%) of granule surface area at a binder concentration of 10% w/w corresponded to similar optima in friability, compressability and median granule size. Surface and pore-void structural analysis by mercury intrusion could not discriminate between pore-void sizes in the range 0.5–100 nm. Nitrogen adsorption measurements showed, however, that the microporous surface area decreased from 0.3 to 0.18 m2 g−1 as binder surface coverage increased over the concentration range 2 to 20% w/w starch mucilage.
Isolation and identification of a fluorophore from ampicillin degradation
Authors: Lebelle M J , Vilim A , Wilson W L 
Published: April 2011

Abstract
A fluorescent impurity in ampicillin has been isolated and identified as 2-hydroxy-3-phenyl-pyrazine. The product is formed under acidic conditions similar to those employed in some fluorometric assay procedures. The mechanism of the reaction is proposed to involve cyclization by condensation of the penilloaldehyde of ampicillin. The structure was confirmed by independent synthesis.
The detection of enzyme induction by rat liver microsomes prepared by isoelectric precipitation
Authors: Parkinson Andrew , Safe Stephen 
Published: April 2011

Abstract
A comparison was made of various indices of the hepatic drug-metabolizing apparatus associated with the postmitochondrial supernatant, microsomes harvested by differential centrifugation, and microsomes harvested by isoelectric precipitation from control, phenobarbitone-pretreated and 3-methylcholanthrene-pretreated rats. The metabolic capabilities and distinctions between control and induced rats for each of the three liver preparations compared favourably as determined by the concentration of cytochrome b5 and P-450 and by the activity of NADPH-cytochrome c reductase, 4-dimethylaminoantipyrine N-demethylase and aryl hydrocarbon (benzo[a]pyrene) hydroxylase. The results suggest that the relatively simple isoelectric precipitation technique is a useful alternative to the conventional method of differential centrifugation for the preparation of hepatic microsomes.
A radioreceptor assay for benzodiazepines
Authors: Hunt Peter , Husson Jean-Marc , Raynaud Jean-Pierre 
Published: April 2011

Abstract
A simple, rapid and sensitive radioreceptor assay for determining benzodiazepines in serum is based on the displacement by the drug of specific [3H]diazepam binding to a membrane fraction from rat brain. The limit of detection of the more active benzodiazepines is about 0.5 ng. Diazepam, nitrazepam, clobazam and HR 458t have been assayed in human serum after a single oral clinical dose. The results can be used for determining pharmacokinetic parameters. The technique measures not only the parent benzodiazepine but also clinically active metabolites.
Determination of erythrocyte membrane-buffer partition coefficients by numerical analysis of multicomponent spectra
Authors: Grìnbauer H J M , Bultsma T , Bijloo G J , Rekker R F 
Published: April 2011

Abstract
A method suitable for the measurement of erythrocyte membrane-buffer partition coefficients by u.v.-spectrophotometry is described. This method is characterized by a proper correction for inconstant background absorption in case of bad signal to noise ratios. For this purpose the multicomponent u.v.-spectrum of a compound in the presence of absorbing materials lost by erythrocyte membranes is decomposed into its constituent spectra by means of numerical analysis. Application of this method to the determination of partition coefficients of benzhydrol, 4-bromophenol and benzyl alcohol yields satisfactory agreement with literature values for the latter two coefficients.
An in vitro study of the effects of calcium on the cardiovascular actions of thiopentone, Althesin and ketamine in the rat
Authors: Hall P J , Pleuvry Barbara J 
Published: April 2011

Abstract
The actions of three intravenous anaesthetics, Althesin, thiopentone and ketamine have been compared on the rat isolated atria and portal vein. Although the three anaesthetics had grossly similar actions on the two preparations, i.e. depression of atrial rate and depression of the amplitude of myogenic activity in the portal vein, there were enough differences to suggest that they produced their effects by different mechanisms. These differences were particularly obvious in interactions with noradrenaline and the effects of changes in calcium ion concentration on the concentration effect relationships for the agents on the atria and portal vein. Generally Althesin was unaffected by changes in calcium ion concentration, whilst ketamine and thiopentone were affected, but in qualitatively different ways.
Role of taurine as a possible transmitter in the thermoregulatory pathways of the rat
Authors: Win R W Ker , Pycock C J 
Published: April 2011

Abstract
Taurine (10 and 20 μg) injected unilaterally into the lateral ventricle of rats caused an increase in core temperature. Bilateral injection of taurine 2.5 and 5 into the preoptic region of the anterior hypothalamus induced a dose-related hyperthermia: higher doses (10 μg) caused hypothermia. Intrahypothalamically taurine-induced hyperthermia was blocked by prior injection of strychnine hydrochloride (5 and 15 μg); doses which alone had no effect on core temperature. Of the other inhibitory amino acids injected intrahypothalamically hypotaurine also induced a hyperthermia. GABA (10 μg) caused hypothermia; glycine (10 μg) had no effect. Potassium (50 mM) stimulated release of radioactivity from superfused slices of anterior hypothalamus prelabelled with [3H]taurine in a calcium-dependent manner. A high affinity uptake mechanism with a Km of 8.5 μM was demonstrated with [3H]taurine into slices of anterior hypothalamus. Taurine may have a neurotransmitter role in the anterior hypothalamus but whether the body temperature effects represent physiological or pharmacological events remains to be established.
Evaluation of changes in drug particle size during tableting by measurement of dissolution of disintegrated tablets
Authors: Kitamori Nobuyuki , Makino Tadashi 
Published: April 2011

Abstract
Three poorly soluble drugs (chloramphenicol, phenacetin and prednisolone) were compressed into tablets of 10% drug content on a physical testing instrument at three different compression pressures. The dissolution profiles were determined by a modification of the U.S.P. method for drug suspensions, granules before compression, disintegrated and intact tablets. By comparison of the dissolution rates for disintegrated tablets with those for granules before compression, or suspensions, it is possible to separate the change in particle size during compression from the pressure-dependent dissolution behaviour of intact tablets. A comparative measurement of dissolution for disintegrated tablets with that for granules provides a useful method for elucidating the particle bonding or cleavage within the tablet during compression.
Effect of drug content and drug particle size on the change in particle size during tablet compression
Authors: Kitamori Nobuyuki , Makino Tadashi 
Published: April 2011

Abstract
Three size fractions for each of three poorly soluble drugs were compressed into 10 mm diameter tablets of four different dilution ratios. The compression was carried out on a physical testing instrument at four compression levels of 49·0, 98·1, 196·2 and 294·3 MN m−2. The effect of drug content and drug particle size on the change in particle size during tableting was examined by the determination of the dissolution rate for disintegrated tablets. A linear relation was obtained when plotting ***1n(T80%) versus drug content. There was a critical particle size where the phenomena of cleavage and bonding during tableting balanced each other, but this varied with drug content.
Effect of taurine on release of 3H-GABA by depolarizing stimuli from superfused slices of rat brain cerebral cortex in vitro
Authors: Leach Michael J 
Published: April 2011

Abstract
The effect of taurine on potassium (30 mM), veratrine (10 μg ml−1) and ouabain (100 μM) induced release of 3H-GABA from superfused slices of rat brain cerebral cortex has been studied. Taurine (10–100 mM) potentiated K+-induced release of 3H-GABA but was more potent in potentiating veratrine- and ouabain-induced release, having significant effects at 5 mM and 1 mM respectively. The potentiation of stimulus induced release does not appear to be due to inhibition of reuptake and the effect is consistent with both a ‘modulatory’ role and anticonvulsant action for taurine.
The disposition of [14C]metronidazole in rats following vaginal and oral administration
Authors: Buttar H S , Siddiqui W H , Moffatt J H 
Published: April 2011

Abstract
The absorption, tissue distribution and excretion of [14C]metronidazole (14C-MTZ) were compared during the first 4 h after administration of 10 mg kg−1 of 14C-MTZ either orally or intravaginally (i.v.g.) to rats. Peak 14C blood concentrations were reached at 1 h in both groups. Blood samples collected at 0·5, 3 and 4 h had a higher 14C concentration in orally dosed rats (P &lt;0·05) than in i.v.g.-treated animals. About 3% of the i.v.g. applied dose remained in the vagina at 4 h. After 4 h, the plasma, liver, kidney, brain, lung and uterus concentrations of 14C were similar in both groups, whereas the blood, skeletal muscle and fat 14C values were significantly greater in the orally dosed rats. The total recoveries of 14C in the urine and faeces did not differ (ca 38% over 4 h) between the two groups. These results suggest that the kinetics of metronidazole are similar after the administration of equal amounts of this drug by either route.
Dopamine receptor changes after long-term haloperidol treatment in rats
Authors: Ebstein Richard P , Pickholz Dalia , Belmaker Robert H 
Published: April 2011

Abstract
Tardive dyskinesia is a neurological syndrome associated with prolonged neuroleptic treatment of schizophrenic patients (Crane 1968; Faurbye 1970; Faurbye et al 1964). It has been suggested that tardive dyskinesia results from chemical denervation of central dopamine neurons and subsequent development of supersensitivity of the postsynaptic receptor (Rubovits & Klawans 1972). Experiments based on animal models of tardive dyskinesia support this hypothesis. Chronic neuroleptic treatment increases postsynaptic dopamine receptor sensitivity when measured either behaviourally or biochemically (Christensen et al 1976; Klawans & Rubovits 1972; Moore & Thornburg 1975; Sayers et al 1975; Tarsy & Baldessarini 1974; Von Voigtlander et al 1975). The molecular basis for this behavioural change has been reported to be an increase in the number of receptor sites with no change in their affinity as measured by 3H-neuroleptic binding to striatal membrane homogenates (Burt et al 1977; Klawans et al 1977; Muller & Seeman 1977). Previous biochemical reports of the development of model tardive dyskinesia after neuroleptic treatment of animals have generally used treatment periods of 3 weeks or less (Burt et al 1977; Klawans et al 1977; Muller & Seeman 1977). Only one report treated animals for longer periods (Clow et al 1978). In the present experiments we studied the kinetics of [3H]spiroperidol binding to rat caudate nucleus homogenates after 3 and 10 weeks of haloperidol treatment.
The effect of some new antidepressants on apomorphine-induced hypothermia in mice
Authors: Przegalinski E , Bigajska K , Siwanowicz J 
Published: April 2011

Abstract
Imipramine-like tricyclic antidepressants antagonize hypothermia induced by apomorphine in mice (Lapin & Samsonova 1968; Schelkunov 1968, 1977; Fuxe & Sjöqvist 1972; Maj et al 1974; Puech et al 1978); this phenomenon has been used by some authors as a test for the antidepressant activity. Therefore, we have examined the effect of some new antidepressants in this test, especially as some of them differ in their mechanism of action from imipramine-like drugs. The drugs used were: nomifensine, an inhibitor of the dopamine and noradrenaline (NA) uptake (Hunt et al 1974; Schacht & Heptner 1974), two specific inhibitors of 5-hydroxytryptamine (5-HT) uptake, femoxetine (FG 4963) (Buus Lassen et al 1975) and poroxetine (FG 7051) (Petersen et al 1977), two other antidepressants whose main characteristic was the blockade of central 5-HT receptors, i.e. mianserin (van Riezen 1972) and trazodone (Baran et al 1979). We also included pizotifen, a drug used in migraine prophylaxis (see Speight & Avery 1972) but exerting an antidepressant effect (Standal 1977; Banki 1978) and a potent central anti 5-HT activity (Dixon et al 1977; Przegalinski et al 1979). For comparison, the effect of four tricyclic antidepressants (imipramine, desipramine, amitriptyline and chlorimipramine) was also studied.
Haemodynamic effects of the carboxylic ionophore monensin when administered before and during shock induced by E. coli endotoxin
Authors: McCaig Dorothy J , Parratt J R 
Published: April 2011

Abstract
The haemodynamic effects of the carboxylic ionophore monensin have been examined in cats anaesthetized with sodium pentobarbitone. Marked increases in left ventricular dP/dtmax (and dP/dt at fixed isovolumic pressures) and slight increases in cardiac output and stroke volume occurred, indicating increased myocardial contractility. Heart rate was unchanged but systemic arterial pressure was substantially increased. Satisfactory increases in contractility and arterial pressure were obtained when monensin was infused intravenously in a total dose of 0·25 mg kg−1 over 10 min. Larger doses, especially if rapidly injected, resulted in very marked increases in myocardial contractility leading eventually to cardiac failure. The haemodynamic effects of monensin were markedly reduced during shock induced by E. coli endotoxin and there was unfortunately no evidence to suggest that this extremely potent compound might be potentially beneficial in this form of profound cardiovascular shock.
Non-competitive-non-equilibrium α-adrenoceptor blocking properties of N-benzyl iodoacetamide, betsamide
Authors: Huidobko-Toro J Pablo , Huidobro F , Miranda H 
Published: April 2011

Abstract
N-Benzyl iodoacetamide, betsamide, at 10 mg kg−1 i.v. blocked the hypertensive and contractile responses of the nictitating membrane of the cat to adrenaline. The blockade had a lag period before full development. Pretreatment of cats with betsamide for 7 or 18 h showed a non-equilibrium type of α-adrenoceptor blockade. The responses of the nictitating membrane to adrenaline were markedly depressed and did not recover after high doses of adrenaline. In the same cats, adrenaline caused a profound hypotension. The effect of betsamide lasted for at least 72 h. In the rat isolated vas deferens, 3 times 10−5 M betsamide non-competitively blocked the contractile responses to noradrenaline; the adrenoceptor blockade was less effective when betsamide was applied with noradrenaline. The blockade lasted for more than 24 h, and was not reversible after extensive washing. Betsamide antagonized the contractile effects of carbachol and 5-hydroxytryptamine on the rat vas deferens, but not the β-responses of the guinea-pig trachea to adrenaline and isoproenaline. Results are discussed in relation to a probable mechanism of action.
Potentiation of the diabetogenic effect of streptozocin by phentolamine in the rat
Authors: Walker P K Tal , Kaul C L , Grewal R S 
Published: April 2011

Abstract
The effect of α- and β-adrenoceptor blocking agents and a β2-agonist, salbutamol, on the diabetogenic effects of streptozocin (threshold doses) was investigated in the rat. Phentolamine and salbutamol potentiated the diabetogenic effect of streptozocin but phenoxybenzamine, tolazoline, Oxprenolol and propranolol were without effect. The potentiating effect of phentolamine was blocked by Oxprenolol. Potentiation of the diabetogenic effect by phentolamine is not related to α-adrenoceptor block, vasodilatation or insulin release. But it may be related to its ability to stimulate β-adrenoceptors.
Effect of 5-hydroxytryptamine on blood glucose and cyclic AMP in the rat
Authors: Itaya Koichi , Itoh Madoka 
Published: April 2011

Abstract
The effects of 5-hydroxytryptamine (5-HT) on plasma cyclic AMP (cAMP) and glucose concentrations were studied in rats in vivo. 5-HT injected i.p. increased plasma cAMP and glucose. Injections of propranolol, hexamethonium, and cyproheptadine inhibited the 5-HT-induced increase in glucose but not in cAMP. Atropine did not inhibit the action of 5-HT. These effects of 5-HT were not seen in adrenomedullectomized rats, and 5-HT did not elevate the concentration of plasma cAMP in anti-glucagon antiserum-injected rats. These results confirm the previously reported finding that 5-HT-induced increase in blood glucose is mediated via adrenaline released from adrenal medulla by 5-HT and suggest that the increase in plasma cAMP, induced by 5-HT, is due to glucagon released by an unknown factor, or factors other than adrenaline released from the adrenal medulla by 5-HT.
Dissolution of bupivacaine 3-hydroxy-2-naphthoate into phosphate buffers
Authors: Nakano Naomi I , Setoya Akiko 
Published: April 2011

Abstract
Dissolution behaviour of bupivacaine 3-hydroxy-2-naphthoate (BUPNH) into phosphate buffers, pH 7·4 was investigated at 25° and 37°C. Although the dissolution pattern of the salt at 25°C was normal, i.e. the concentrations of the acid and base component agreed, during the entire dissolution period, that at 37°C was anomalous. The dissolution consisted of two phases, i.e. an initial normal phase was followed by a second slower phase in which the concentration of the acid became, at equilibrium, markedly higher than that of the base. This unusual dissolution behaviour at 37°C was shown to be due to the precipitation of the base, which, in turn, is attributed to the unusual temperature dependency of the solubility of the base in phosphate buffers, i.e. decrease in solubility with increasing temperature.
An in vitro model for assessing drug availability from lipophilic vehicles
Authors: Armstrong N A , James K C , Wong C K 
Published: April 2011

Abstract
An apparatus for studying the rate of release of a solute from a water-immiscible solvent into an acidic, aqueous liquid, followed by permeation through a simulated lipid membrane, is described. The object was to imitate the absorption of a drug after oral administration in a soft gelatin capsule. Rate constants of transfer were determined for a series of substituted benzoic acids, using octanol and isopropyl myristate as solvents. The quantity of solute in the acidic phase did not correlate with the solvent-water distribution coefficient, but was linearly related to the rate constant for transfer from solvent to water. A dynamic system was therefore postulated, rather than one in which the two phases are in equilibrium. In vivo studies on two of the solutes confirmed the in vitro observations. No simple relationship could be derived between blood concentrations and any in vitro parameter, but the rank order of magnitude of the blood concentrations fitted the postulated dynamic mechanism.
Precise spectrophotometry of small quantities of drugs in the presence of irreproducible quantities of impurities
Authors: Vezin W R 
Published: April 2011

Abstract
A variety of methods of spectrophotometric assay of compounds in the presence of one or more irrelevant impurities have been recently described, employing, for example, the use of Legendre polynomials and trigonometric functions. The use of least-squares solutions of overdetermined systems (Scheid 1968) in spectrophotometry is outlined, with conditions under which simplified overdetermined systems have been used for precise spectrophotometric assay of small quantities of drug substances in the presence of largely irreproducible quantities of irrelevant impurities.
Effect of ricinoleic acid and other laxatives on net water flux and prostaglandin E release by the rat colon
Authors: Beubler E , Juan H 
Published: April 2011

Abstract
Ricinoleic acid, oleic acid, dioctyl sodium sulphosuccinate, deoxycholic acid, sennoside A + B and mannitol reduced or reversed water flux from lumen to blood in rat colon in situ. Stearinic acid was without any effect. Ricinoleic acid, oleic acid, dioctyl sodium sulphosuccinate, deoxycholic acid and sennoside A + B stimulated release of PGE-like material into the colonic lumen whereas the osmotic laxative mannitol and stearinic acid did not. Inhibition of PGE biosynthesis by pretreatment of the rats with indomethacin significantly reduced (but did not abolish) the effect of ricinoleic, oleic and deoxycholic acids on net water flux and PGE release. Indomethacin reduced the effect of dioctyl sodium sulphosuccinate and of sennoside A + B on PGE release but not their effect on the net water flux. The effect of mannitol was not influenced by indomethacin. The amount of PGE release in experiments with ricinoleic acid, oleic acid, stearinic acid and dioctyl sodium sulphosuccinate (with and without indomethacin) showed a good correlation (r = 0·99) with the change in net water flux. Deoxycholic acid, sennoside A + B and mannitol did not show this correlation. It is assumed that the action of non-osmotic laxatives is partially mediated by PGE, although other mechanisms also seem to be involved in their mode of action.