bluuebunny/crossref_metadata_2025_split huggingface dataset:
Generated surface area measurement of disintegrating tablets
Authors: Rubinstein Michael H , Wells James I 
Published: April 2011

Abstract
The surface areas generated by the disintegration and dissolution of six commercial brands of phenylbutazone tablets B.P. 100 mg have been measured using a Model Ta Coulter Counter. The graphs of surface area generated against time were all of the same shape and always reached a maximum value. The initial surface area increase was due to tablet disintegration and deaggregation and followed first order kinetics. A good correlation between the slope of this initial increase and disintegration time was found. The maximum surface area generated correlated at the probability level of better than 99·9% with the dissolution rate measured as t60. The subsequent decrease in surface area, after this maximum, was considered to be due to phenylbutazone dissolution and was also first order rate controlled.
Effect of a second solubilizate on the partition coefficient of drugs in micellar solution and their permeation rate across an artificial membrane
Authors: Alhaique F , Giacchetti D , Marchetti M , Riccieri F M 
Published: April 2011

Abstract
The distribution of a solubilizate between micelles and the aqueous phase does not obey a simple partition law when a second solubilizate species is present. Alterations of the apparent partition coefficient cannot be explained in terms of a simple displacement mechanism, following the interaction of both solubilizates with the same site of the micelle. A non linear increase in solubilizate association to micelles following an increase in surfactant concentration is observed in the presence of a second solubilizate. A depression in the cloud point temperature follows the addition of a second species and is such that cannot be interpreted as a simple additive effect. Alteration of the apparent partition coefficient in a micellar solution has an effect on the permeation rate of the solubilizate across an artificial membrane. Bio-pharmaceutical implications are discussed.
Metabolic oxidation of aralkyl oximes to nitro compounds by fortified 9000g liver supernatants from various species
Authors: Beckett A H , Jones G R 
Published: April 2011

Abstract
Incubation of ‘amphetamine oxime’ (IIa, anti-benzyl methyl ketoxime) with fortified rabbit liver 9000 g supernatants gave the nitro compound (Ie) and the β-hydroxylated oxime (IIc) in addition to the previously reported ketone (IIb) and alcohol (Ic) metabolites. Formation of the products was cofactor dependent. The nitro compound was also formed using mouse, hamster and guinea-pig 9000 g liver supernatants and to a minor extent by rat liver. The oximes of 2-phenethylamine (IIe) and norfenfluramine (IIg) were also metabolized to the corresponding nitro compounds, ketones and alcohols with rabbit 9000 g liver supernatants; however, no nitro compound (IIIb) was detected after the incubation of ‘mexiletine oxime’ (IVa). The metabolic products were identified and characterized by g.l.c., t.l.c. and g.l.c. linked mass spectrometry by comparison with synthetic materials.
Dopamine receptors in rat striatum and nucleus accumbens; conformational studies using rigid analogues of dopamine
Authors: Woodruff G N , Watling K J , Andrews C D , Poat Judith A , McDermed J D 
Published: April 2011

Abstract
A study was made of the actions of dopamine and of some 2-amino-1,2,3,4-tetrahydronaphthalenes on dopamine-sensitive adenylate cyclase in homogenates of rat striatum and nucleus accumbens. The compounds were also tested for their ability to stimulate motor activity following bilateral injection into the nucleus accumbens of conscious rats. The most active compounds on adenylate cyclase from both striatum and nucleus accumbens were dopamine and 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene(6,7-diOHATN). The 5,6-dihydroxy analogue (5,6-diOHATN) was 50 times less active than 6,7-diOHATN in striatal homogenates and 350 times less active in homogenates of nucleus accumbens. All dihydroxy compounds tested were active in causing stimulation of motor activity, the most active compounds being 6,7- and 5,6-diOHATN. Both dimethoxy derivatives tested were inactive on the adenylate cyclase and as locomotor stimulants.
Interpretation of dissolution rate data from in vitro testing of compressed tablets
Authors: Kitazawa Shikifumi , Johno Ikuo , Minouchi Tokuzo , Okada Jutaro 
Published: April 2011

Abstract
To find if theoretically and experimentally a relation existed between the dissolution rate theory of Kitazawa, Johno & others (1975) and that of Wagner (1969), a study was undertaken with uncoated caffeine, aspirin and proxyphylline tablets using two dissolution methods. Although the original treatment for surface area of drug available for dissolution was quite different between the two dissolution theories, the dissolution rate constants obtained were in fair agreement. Hence it might not be always necessary to take into consideration changes in the surface area as a function of dissolution rate, and the 1n W∞/ (W∞ - W) versus time plot devised by Kitazawa & others might be a useful and simple means of obtaining the dissolution rate constant of an active ingredient from a dosage form such as compressed tablet.
Cannabinoid patterns in seedlings of Cannabis sativa L. and their use in the determination of chemical race
Authors: Rowan M G , Fairbairn J W 
Published: April 2011

Abstract
We have examined the cannabinoid contents of seedlings from twelve strains of Cannabis of known chemical race. Fourteen days after emergence of the shoot those of the tetrahydrocannabinol (THC) type could be distinguished from those of the cannabidiol (CBD) type. The true leaves of the THC type contained a relatively high content of THC and also contained cannabichromene (CBC), sometimes as the major cannabinoid, whereas the CBD type had much lower amounts of THC and no CBC; CBD being the major component. A strain from China corresponded to the THC type but showed some unusual features. Seeds purchased at seven outlets in Britain were also examined. Only two batches germinated but these proved to be of a THC type and resembled the Chinese strain.
Increasing the probability of sterility of medicinal products
Authors: Brown M R W , Gilbert P 
Published: April 2011

Abstract
Calculations show that official tests for sterility offer unacceptably low degrees of assurance of sterility. Some batches of heat treated articles with 10% contamination can pass the E.P. test on about 92% of occasions. It is proposed that viable counts be made on products immediately before the terminal inactivation procedure and that upper limits be set for the level of contamination. Samples of the product should be inoculated with spores of known resistance characteristics and also with samples of swabs from the production area. Such inoculated products should then be tested for absence of viable organisms, after being subjected to the terminal inactivation procedure. This test should be coupled with close environmental and process control and personnel education. It is recommended that these procedures replace the conventional test for sterility. The use of spores as direct and independent indicators of sterility, especially where the lethal conditions cannot be monitored instrumentally is recommended. A flexible approach is proposed for the use of the ‘lethality factor’ suitable for a terminal heat inactivation procedure; this would depend on the nature of the product and the standard of monitoring facilities and personnel. A change in the language is proposed. A medicinal product processed such that an acceptable probability of sterility exists, should be designated not as sterile but as safe.
The dissolution mechanism in a system undergoing complexation: salicylamide in caffeine solution
Authors: Donbrow M , Touitou Elka 
Published: April 2011

Abstract
The dissolution rate of compressed salicylamide discs has been measured in water and in caffeine solutions of increasing concentration at 15, 25, 37 and 45° in an apparatus rotating at 48 rev min−1 or more. Dissolution rate profiles showed breaks indicative of a shift in the mechanism of dissolution from interfacial towards transport control. The shifts occurred at higher caffeine concentrations on increasing the agitation rate or temperature. The dependencies of dissolution rates on agitation rates typified the intermediate type of dissolution and Arrhenius plots indicated that interfacial and transport processes participated in salicylamide dissolution.
Relaxations mediated by adrenergic and non-adrenergic nerves in human isolated taenia coli
Authors: Stockley Helen L , Bennett Alan 
Published: April 2011

Abstract
In human taenia coli electrical field stimulation after cholinergic blockade excited mainly non-adrenergic inhibitory nerves. Adrenergic relaxations during stimulation were demonstrated only with short electrical pulses at high frequencies or with ganglion stimulants. Reduction by tetrodotoxin of relaxations to indirectly acting sympathomimetics supports the histochemical finding that colonic adrenergic nerves are mainly preganglionic, and possibly synapse with non-adrenergic inhibitory nerves. When the latter undergo direct maximal stimulation, responses to adrenergic nerve excitation are masked.
Evidence for more than one type of 5-hydroxytryptamine receptor in the human colon
Authors: Burleigh D E 
Published: April 2011

Abstract
The actions of methysergide, a 5-hydroxytryptamine (5-HT) antagonist, have been examined on muscle strips taken from the circular and longitudinal layers of the human colon. Relaxations of the longitudinal muscle to 5-HT were antagonized by concentrations of methysergide known to be selective. Relaxations of the circular muscle to 5-HT were unaffected by similar concentrations of methysergide. Responses of both types of muscle to 5-HT were partially reduced by tetrodotoxin. Furthermore there was evidence for 5-HT receptors in circular colonic muscle which were unaffected either by selective concentrations of methysergide or tetrodotoxin.
Analysis of the β-receptor mediated effect on slow-contracting skeletal muscle in vitro
Authors: Waldeck Bertil 
Published: April 2011

Abstract
Subtetanic contractions of the guinea-pig isolated soleus, a slow-contracting skeletal muscle, were evoked by transmural field-stimulation. Isoprenaline caused a dose-dependent depression of the contractions. This effect was inhibited by propranolol and H 35/25 (1-(p-tolyl-2-isopropylamino-1-propanol) but not by practolol. Similar results were obtained for terbutaline. Tazolol and H 80/62 (1-isopropylamino-3-(p-hydroxyphenoxy)-2-propanol HCl), selective β1-agonists, had no effect per se but inhibited the effect of terbutaline. Adrenaline, noradrenaline, and dopamine all caused a dose-dependent decrease in the force of the soleus contractions, their potencies being in that order. Tyramine did not appreciably affect the contractions nor did it inhibit the effect of terbutaline. Pretreatment with reserpine, if anything, increased the response to terbutaline. It is concluded, in conformity with previous in vivo studies, that the adrenergic receptor mediating the effect on the soleus muscle contractions is of the β2-type. Indirect sympathomimetic effects do not contribute to the responses observed on the isolated soleus muscle.
A comparison of the dissolution rates of caffeine tablets in a rotating-basket with those in a Sartorius dissolution tester
Authors: Kitazawa Shikifumi , Johno Ikuo , Minouchi Tokuzo , Ito Yoko , Okada Jutaro 
Published: April 2011

Abstract
Uncoated caffeine tablets of four different hardnesses were tested for dissolution rate by the Sartorius (S.S. method) and by the rotating basket method of the U.S.P. XVIII. In both methods the dissolution rate decreased with increasing hardness, and the rate obtained with the S.S. method was always less than that by the U.S.P. method. This result cannot be explained as being due only to the difference in the volume of dissolution medium. Also it was difficult to ensure that the characteristic changes in the process of dissolution paralleled the curves obtained from a plot of % caffeine dissolved vs time. Accordingly, the dissolution rate constants were calculated from the slope of each straight line in a plot of In W∞/(W∞ - W) vs time.
The effect of age and thyroid hormones upon the ability of the chick heart to deaminate monoamines
Authors: Fowler C J , Callingham B A 
Published: April 2011

Abstract
The effect of age and thyroid hormones upon the ability of chick heart homogenates to metabolize monoamines has been investigated. 5-Hydroxytryptamine is entirely metabolized by a monoamine oxidase (MAO) with the characteristics of MAO-A, whereas some of the tyramine and all of the benzylamine are oxidatively deaminated by a clorgyline-resistant, but semicarbazide-sensitive enzyme, with a similar subcellular distribution to that of MAO. The remainder of the tyramine deamination is brought about by MAO-A and MAO-B. The specific activities of both clorgyline-sensitive and resistant enzymes are increased by the same proportion by increase in age or by treatment with (-)-thyroxine, and decreased by 2-thiouracil. The significance of these results is discussed.
The central and peripheral effectiveness of two oxotremorine-antagonists determined using oxotremorine-induced tremor and salivation
Authors: Eicholzer Alfred , Ögren Sven-Ove 
Published: April 2011

Abstract
Two oxotremorine antagonists have been examined using oxotremorine as the tremor and salivation inducer and the ratios between the central and peripheral nervous systems determined. Under these conditions these compounds are still more effective antagonists centrally than peripherally. Differences in distribution to the various muscarinic receptors involved is believed to be the major factor in determining this separation of central and peripheral activities.
A model for the selective mode of action of the irreversible monoamine oxidase inhibitors clorgyline and deprenyl, based on studies of their ability to activate a Ca2+-Mg2+ ATPase in defined lipid environments
Authors: Houslay Miles D 
Published: April 2011

Abstract
Clorgyline and deprenyl activated the pure Ca2+-Mg2+ ATPase from rabbit muscle sarcoplasmic reticulum when it was in a defined lipid environment of either dimyristoyl lecithin or dipalmitoyl lecithin, apparently by fluidizing the phospholipid that surrounds the protein (the phospholipid annulus). Activation was only significant at temperatures when the annulus placed rigid constraints upon the protein. There was a two order of magnitude difference in the concentration at which the drugs achieved their effect which is thought to be related to their abilities to perturb the phospholipid annulus since it could not be attributed simply to the small differences in their partition coefficients. Clorgyline, which was more potent than deprenyl at effecting fluidization of the phospholipid annulus of the Ca2+-Mg2+ ATPase in the defined lipid environments, activated species ‘B’ monoamine oxidase at concentrations at which it began to inhibit the species ‘A’ enzyme. Deprenyl did not activate the species ‘A’ enzyme at any concentration tested. It is suggested that, in tissues where there are multiple forms of mitochondrial monoamine oxidase, the selective action of clorgyline and deprenyl arises from a modification of the single inhibitor binding site on a protein species to yield species ‘A’ enzyme and species ‘B’ enzyme. One form of this modification to give the species ‘A’ monoamine oxidase would be a masking of the inhibitor binding site by lipid such that it could be readily penetrated by clorgyline but less readily so by deprenyl. The other form of the modification would yield the species ‘B’ enzyme, which like the ‘chaotrope-treated’ enzyme and presumably ‘nascent’ monoamine oxidase, would expose the inhibitor binding site to the aqueous environment in which deprenyl would be the more efficacious inhibitor.
The effect of metyrapone on granuloma induced by carrageenan-impregnated sponges in normal and essential fatty acid deficient rats
Authors: Parnham M J , Adolfs M J P , Bonta I L 
Published: April 2011

Abstract
Treatment of normal rats with metyrapone (20 mg kg−1 day−1, s.c.) for 5 days, starting on the day before implantation, inhibited the production of granuloma, induced by carrageenan-impregnated sponges, determined 8 days after implantation. Exudate volume and prostaglandin (PG) production were unaffected. In essential fatty acid deficient (EFAD) rats, metyrapone did not alter the already existing adrenal hyperplasia due to EFAD and did not affect either granuloma formation or exudate production. The results are discussed in relation to earlier work using adrenalectomy and with regard to the effect of EFA deficiency on adrenal corticosteroid production. It is suggested that metyrapone is a more useful tool than adrenalectomy in studying the role of endogenous corticosteroids.
Platelets in inflammatory exudates
Authors: Bolam J P , Smith M J H 
Published: April 2011

Abstract
In exudates of implanted sponges in the rat there are apparent accumulations of blood platelets, assessed by the light microscope, and of radioactivity from labelled platelets administered systemically. The use of more specific techniques for platelet detection showed no evidence of intact blood platelets in the exudate and the radioactivity was not associated preferentially with cellular components in the exudate.
Permeability of human epidermis to phenolic compounds
Authors: Roberts M S , Anderson R A , Swarbrick J 
Published: April 2011

Abstract
The permeability of human epidermis to many phenolic compounds can be related to octanol/water partition coefficients. For a series of compounds having similar diffusion coefficients and showing an increase in lipophilic character, the maximum flux will be obtained with the less lipophilic compounds because the solubility decreases more rapidly than the partition coefficient increases. The penetration of some phenolic compounds is concentration dependent, a constant permeability coefficient being observed below a threshhold concentration above which the permeability coefficient increases with concentration. The increase in the permeability coefficient is attributed to ‘damage’ to the epidermis and a reduction in its diffusional resistance. A relation between the ability of a substance to damage the skin and the lipophilic character (or more generally the penetration flux) of the substance was found. A number of substances do not appear to ‘damage’ the skin due to insufficient substance partitioning or penetrating into the stratum corneum. This ‘cut-off’ in effect is generally observed for the more lipophilic substances. For a series of compounds, maximum damage will be obtained with the less lipophilic compounds in accordance with the predicted concentrations of the substance in the stratum corneum. Phenolic compounds appear to interact with the skin by protein denaturation although for the more lipophilic compounds some degree of ‘plasticization’ of the lipids is evident.
Estimation of the degree of crystallinity in digoxin by X-ray and infrared methods
Authors: Black D B , Lovering E G 
Published: April 2011

Abstract
The X-ray procedure for estimation of the degree of crystallinity in digoxin is based upon measurement of the total X-ray scattering and the scattering from crystalline regions of the drug. The infrared procedures are based upon measurement of the peak height ratios, 1775/1618 and 3095/1618 cm−1. Correlation between results obtained by the two methods is good. These methods are of value in the physico-chemical characterization of digoxin, particularly as the properties may be altered by comminution.
The effect of composition and ageing on the dissolution rates of chlorpropamide-urea solid dispersions
Authors: Ford James L , Rubinstein Michael H 
Published: April 2011

Abstract
Discs of chlorpropamide and urea have been prepared by (a) melting and (b) compression. Intrinsic and relative dissolution rates of the discs have been measured and the dissolution process investigated microscopically. Higher dissolution rates were found from melts than from physical mixes. The optimum dissolution rate composition found was for a melt composed of 30% w/w chlorpropamide which possessed an intrinsic dissolution rate 930 times greater than for the pure drug. Sphere formation, during dissolution rate measurement has been observed and a likely mechanism proposed to account for its occurrence. Dissolution rates generally increased with age for most melt compositions.
The effect of bromocriptine on locomotor activity and cerebral catecholamines in rodents
Authors: Dolphin A C , Jenner P , Sawaya M C B , Marsden C D , Testa B 
Published: April 2011

Abstract
The locomotor activity in mice induced by bromocriptine was suppressed by drugs inhibiting both dopaminergic and noradrenergic pre- and post-synaptic actions. The onset of locomotor activity was preceded by a period of decreased activity which lengthened with increasing dose. Both increased and decreased turnover of noradrenaline and decreased turnover of dopamine was shown by measurement of the dopamine metabolites homovanillic acid, dihydroxyphenylacetic acid (DOPAC) and the noradrenaline metabolite MOPEG-SO4 and following pretreatment of animals with α-methyl-p-tyrosine. The increased activity caused by bromocriptine did not correlate with a consistent biochemical change, but the period of behavioural suppression appeared to be associated with an increased noradrenaline turnover. Bromocriptine potently inhibited the noradrenaline-stimulated adenylate cyclase system from mouse limbic forebrain suggesting that the increased in vivo turnover of noradrenaline may be due to a post-synaptic receptor blockade. The involvement of cerebral dopamine receptors was substantiated by the ability of bromocriptine to displace [3H]haloperidol from binding sites in rat striatal preparations. The findings are interpreted as indicating a complex involvement of both noradrenaline and dopamine pre-and post-synaptic components in the locomotor activity produced by bromocriptine, possibly due to the involvement of a partial agonist action or an active metabolite.
Changes in vascular reactivity in experimental hypertensive animals following treatment with indapamide
Authors: Finch L , Hicks P E , Moore R A 
Published: April 2011

Abstract
Indapamide at doses of 8–16 mg kg−1 day−1, orally, lowered arterial blood pressure (9–26 mm Hg) in conscious renal hypertensive cats during a two week treatment period. The antihypertensive effect was sustained for 5–7 h after dosing and was not accompanied by reflex tachycardia. Antihypertensive responses to injection of clonidine (20 μg, i.c.v.) were significantly enhanced one week after the completion of indapamide treatment but had returned to normal two weeks later. In DOCA/saline hypertensive rats, administration of indapamide 10 mg kg−1 day−1, orally, or hydrochlorothiazide, 5 mg kg−1 day−1, intraperitoneally, for 10 days produced similar falls in blood pressure (40–45 mm Hg) as measured by an indirect method. Pressor responses to intravenous noradrenaline or tyramine or electrical stimulation of the sympathetic outflow in the pithed rat preparation were much reduced by pretreatment with indapamide (10 mg kg−1, orally) for 10 days. However, cardiovascular reactivity was unaffected by hydrochlorothiazide pretreatment (5 mg kg−1 day−1, i.p.). Isolated perfused mesenteric artery***/preparations from indapamide-treated rats showed no changes in reactivity to noradrenaline, 5-hydroxytryptamine or adenosine-5′-triphosphate from those of control DOCA/saline hypertensive rats. Isolated portal veins from rats pretreated with indapamide showed contractile responses to noradrenaline similar to those of control animals although the frequency of spontaneous contractions was reduced in the former group. The results support a vascular site of action for indapamide and suggest a mode of action different from that of hydrochlorothiazide.