bluuebunny/crossref_metadata_2025_split huggingface dataset:
An anomalous effect of the intermediate products of riboflavine photolysis on the intestinal absorption of poorly absorbed water-soluble drugs in rats
Authors: Ghazy F S , Kimura T , Muranishi S , Sezaki H 
Published: April 2011

Abstract
The influence of the intermediate products of riboflavine photolysis on the absorption of poorly absorbed water-soluble drugs from the rat small intestine has been examined using an in situ recirculation technique. The absorption of phenol red, bromphenol blue (BPB) and their biliary excretion, and lactose isonicotinoyl-hydrazone (lactose-INH) and its plasma concentration were increased in experiments made in the presence of light in contrast to others made in the dark. The absorption of both phenol red and lactose-INH were concentration-dependent. On the other hand, a saturation phenomenon was demonstrated when the concentration of phenol red was kept constant while that of the water-soluble compound flavine mononucleotide (FMN) was changed. The results which were obtained from pretreatment experiments suggest an alteration in the permeability of the intestinal membrane. No enhancement effect could be demonstrated for lumichrome in the presence or absence of light.
The effect of waxes, hydrolysed gelatin and moisture on the compression characteristics of paracetamol and phenacetin
Authors: Obiorah B A , Shotton E 
Published: April 2011

Abstract
Stearic acid or hard paraffin added to crystals of paracetamol and phenacetin reduced capping of tablets prepared by direct compression but did not produce acceptable tablets because the inter-particular bonds were very weak. The pressure cycle that can be constructed from the measurement of the axial pressure and the corresponding die wall pressures offers information that is useful in the formulation of tablets. The behaviour of paracetamol or phenacetin and their mixtures with gelatin hydrolysate or water or both shows a similarity to a Mohr body and it appears that the maximum die wall pressure is affected by the particle size of the material compressed and also by the additives present. Good transmission of radial force implies that the material can be initially consolidated, but alone it does not indicate that the tablet formed is physically stable. When the tablet formed remains coherent after the axial pressure is removed the residual die wall pressure remains high. Measurement of the residual die wall pressure might therefore be a useful indicator for identifying satisfactory formulations of substances that cap readily. Hydrolysed gelatin or water or both together produced paracetamol and phenacetin mixtures with satisfactory compression characteristics.
Data point weighting in pharmacokinetic analysis: intravenous paracetamol in man
Authors: Clements J A , Prescott L F 
Published: April 2011

Abstract
Compartmental analysis of plasma paracetamol concentrations following intravenous injection of 12 mg kg−1 in aqueous solution to normal subjects was performed using analogue and digital computer methods. Using a ‘simplex’ non-linear optimization procedure, the pharmacokinetic parameters were found to be influenced considerably by the choice of the weighting factors (Wi) attributed to individual data points. The plasma half-life of paracetamol varied by up to seven-fold with the weighting factors selected. However, the predicted mean steady-state plasma concentrations were shown to be relatively little affected by the different weighting factors.
A comparison of the binding constant (Kd) of 125I-labelled 3-(4-iodophenoxy)-1-isopropylamino-propan-2-ol obtained on β-adrenoceptors in guinea-pig myocardial membranes, with its dissociation constants (Kb) obtained on guinea-pig isolated atria and trachea
Authors: O'Donnell Stella R , Woodcock Elizabeth A 
Published: April 2011

Abstract
The dissociation constant of binding (KD) of 125I-labelled 3-(4-iodophenoxy)-1-isopropyl-aminopropan-2-ol (IIP) to guinea-pig myocardial membrane preparations was 2·2 × 10−8m. In pharmacological experiments with the non-labelled material and 60 min contact time, IIP produced a parallel shift in the orciprenaline concentration-response line on guinea-pig isolated tracheal and atrial preparations. The dissociation constant (Kb) of IIP was 2·9 × 10−8m on atria (pA2 7·54) and 3·3 × 10−8m on trachea (pA2 7·48). These values indicate that IIP is not a selective β-adrenoceptor blocking drug. In addition, agreement was found between the affinity constant of this antagonist for β-adrenoceptors as determined by a direct binding study and an indirect pharmacological study.
Stimulation of human platelets by carrageenans
Authors: McMillan R M , MaCintyre D E , Gordon J L 
Published: April 2011

Abstract
The rank order of four carrageenans tested as inducers of human platelet aggregation was the same (iota &gt; lambda &gt; gelcarin &gt; kappa) as their relative inflammatory potencies in vivo. All four carrageenans caused some precipitation of plasma proteins, and induced aggregation in platelet-rich plasma or washed platelet suspensions. The second phase of aggregation was citrate-dependent and associated with secretion of 5-hydroxytryptamine and lysosomal enzymes. Platelets could provide a useful model for investigating the actions of carrageenans on cell membranes.
Compactibility of granules prepared by a novel method of granulation and their dissolution
Authors: Ho Tak , Hersey John A 
Published: April 2011

Abstract
Increasing particle size during prolonged grinding by a ballmill has been used as a novel means of producing a pharmaceutical granulation. The compactibility properties of granules of sodium chloride and of paracetamol produced by this method have been elucidated and compared with those produced by conventional granulation techniques. Force-displacement diagrams and double compactions were used to measure the net energy input on tableting. When compared with conventional granulation methods, the agglomerative phase of comminution (APOC) method produced mechanically stronger tablets with a higher dissolution rate than those compacted from granules made by a conventional wet granulation method irrespective of the compaction energy used. Tablet tensile strength is related to the elasticity and yield strength of the substance used. It is suggested that binderless tablets may be prepared using this method, thus simplifying tablet formulation and enhancing stability. A possible mechanism for the increased dissolution rate is the increased internal surface area of the granules produced by the prolonged grinding method.
Thermodynamic parameters of molecular complexes in aqueous solution: enthalpy-entropy compensation in a series of complexes of caffeine with β-naphthoxyacetic acid and drug-related aromatic compounds
Authors: DONBROW M , SAX PHILIP 
Published: April 2011

Abstract
Stability constants and thermodynamic parameters have been evaluated for the complexation reaction in aqueous solution of caffeine with β-naphthoxy acetic acid. The values were higher than those previously reported for the complexation of other ligands with methyl xanthines. In nearly all aromatic ligands complexing with caffeine and theophylline for which data are available, both entropy and free energy of complexation were linearly related to the enthalpy, giving an isoequilibrium relationship. Salicylamide, sodium benzoate and cis-methyl cinnamate exhibited slight deviations on the ΔG-ΔH plot; the non-aromatic dehydroacetic acid showed the largest deviation. The isoequilibrium relationship was shown to be valid statistically (349–365 K, caffeine systems; 353–372 K, caffeine and theophylline systems) indicating underlying chemical causation. Thermodynamic equations are presented for analysis of the factors involved, which are attributed to a combination of substrate-ligand interactions and solvent effects. The substrate-ligand overlap area is considered as a common parameter through which the solvent and interaction forces might cooperate to give rise to linearity in the isoequilibrium relationship. The increasingly negative experimental values of the enthalpy and entropy with increase in ligand planar overlap area are discussed in relation to the underlying forces involved in the complexation.
The influence of gel formulation on the diffusion of salicylic acid in polyHEMA hydrogels
Authors: WOOD J M , ATTWOOD D , COLLETT J H 
Published: April 2011

Abstract
The influence of solute concentration, gel hydration, and crosslinking density on diffusion rates in polyHEMA hydrogels has been investigated using a radio-tracer technique. At hydrations above 31% water, diffusion is by pore flow, and increases in the crosslinking density of gels bring about a decrease in the diffusion coefficient, D. Below 31% hydration, diffusion is predominantly by solution diffusion and changes in crosslinking density have little effect on the diffusion coefficient. The diffusion coefficient is invariant with solute concentration within the range reported, although at a very high solute concentration, for the gels of lower hydration, the diffusion coefficient is higher than expected. A high value for D may be due to saturation of the binding sites of the diffusant on the polymer chains, leaving a greater proportion of diffusant available for transport.
A novel conjugate as a major metabolite of bromperidol in man
Authors: HAWKINS D R , BIGGS S R , BRODIE R R , CHASSEAUD L F , MIDGLEY I 
Published: April 2011

Abstract
The major urine metabolites of the neuroleptic drug, bromperidol, after oral doses to rats and dogs are p-fluorophenylacetic acid and its glycine conjugate resulting from oxidative N-dealkylation. While the same metabolites were also detected in human urine, also present was a major unknown component representing 50% of the total urine metabolites, which apparently was not formed by rats and dogs to any extent. Mass spectroscopic investigations of the metabolite showed that it could be thermally degraded to bromperidol and contained a substituent attached to the tertiary hydroxyl group. The mass spectrum of the metabolite after trifluoroacetylation was consistent with an O-glucofuranosiduronolactone conjugate of bromperidol.
Neurochemical effects of buspirone, a novel psychotropic drug, on the central cholinergic system
Authors: KOLASA K , FUSI R , GARATTINI S , CONSOLO S , LADINSKY H 
Published: April 2011

Abstract
Buspirone, a novel psychotropic anxioselective agent, produced a dose-dependent decrease in the level of acetylcholine in the striatum of the rat. The maximum effect of about 25–30% was produced at the dose of 20 mg kg−1. A smaller decrease of 10% was also found in the n. accumbens-olfactory tubercle while other brain regions were unaffected. The drug did not alter striatal choline acetyltransferase or acetylcholinesterase activities and was feeble in displacing [3H]dexetimide from its specific muscarinic binding sites. The effect of buspirone in lowering acetylcholine content was more marked and longer lasting in the striatum of female than male rats. Buspirone proved to be weak as a blocker of the dopamine receptor agonist, apomorphine, and it appears that only a small proportion of the decrease in striatal acetylcholine content can be attributed to the blockade of dopamine receptors. Rapid homologous tolerance to an acute challenge with buspirone on striatal acetylcholine was achieved within seven days of its chronic administration, and, unlike clozapine, a cross tolerance of buspirone to chronic haloperidol treatment was also observed. Other data indicating that the drug differed from haloperidol both qualitatively and quantitatively on dopaminergic neurochemical parameters, and the fact that it is not cataleptogenic, suggest that buspirone cannot be considered a typical neuroleptic agent. The possibility that buspirone may act as an agonist at certain presynaptic dopamine receptors, which could translate into a fall in striatal acetylcholine content, is discussed.
Determination of porosity variations in powder beds
Authors: WOODHEAD P J , HARDY J G , NEWTON J M 
Published: April 2011

Abstract
A gamma-ray attenuation technique for detecting local porosity variations in packings of pharmaceutical powders has been developed and assessed. It proved necessary to employ an empirical expression describing the attenuation coefficient of the model material, lactose, as a function of porosity. The precision of measurement of local porosity can be pre-selected due to the statistical basis of the method, and local porosity measurements with 95% confidence intervals of ±0.005 can readily be carried out. A method of producing grey-scale images of porosity distributions has been employed to enable the degree of inhomogeneity of a powder bed to be seen.
The relationship between molecular connectivity and partition coefficients
Authors: BOYD J C , MILLERSHIP J S , WOOLFSON A D 
Published: April 2011

Abstract
Kier & Hall (1976) demonstrated that a relationship existed between molecular connectivity and Log P (the Log of the octanol/water partition coefficient) for several classes of compounds and also for the combined classes. This work utilized a number of Log P values calculated using π values. We have reinvestigated this relationship using experimentally determined Log P values. The results confirm Kier & Hall's findings although different connectivity indices are brought into the equations.
Fluidized bed granulation of an ordered powder mixture
Authors: Thiel W J , Nguyen L T 
Published: April 2011

Abstract
The phenomenon of ordered unit segregation is of paramount importance in determining the homogeneity of an ordered mixture. This problem can be avoided by using a monodisperse carrier, but it is uneconomic. The fluidized bed granulation of a 0.1% ordered mixture has been studied as a method of reducing the effects of segregation. The ordered units were stable when fluidized and no significant loss of the microfine adsorbed material occurred during processing. The distribution of the minor component in the granules was significantly more uniform than in the original ordered mixtures. The demixing potential
(where p = proportion of cohesive minor component and w is the weight % of carrier material in a particular size range) was used to quantify the distribution of the minor component as a function of particle size. DP is a coefficient of variation and can be directly compared with the specification standard deviation σA. Batches of granules were compressed into 100 or 350 mg tablets, containing approximately 100 and 350 μg of model drug substance. The weight and content coefficients of variation (c.v.) were determined for 20 tablets. All batches had a weight c.v. ≤1.5% and a content c.v. ≤4.6%. Granulation of an ordered mixture greatly reduces the potential for segregation to decrease the mixture homogeneity. It also provides a solution to the problems which may be encountered when the mixing of small quantities of cohesive materials during conventional fluidized bed granulation is attempted.
Inhibition of prostaglandin E2 release by salicylates, benzoates and phenols: a quantitative structure-activity study
Authors: Habicht J , Brune K 
Published: April 2011

Abstract
Concentrations inhibiting 50% of the prostaglandin E2 release from phorbol ester-stimulated mouse peritoneal macrophages in-vitro were determined for 59 monosubstituted congeners of salicylic acid, benzoic acid and phenol. Twenty-seven further compounds, mainly benzoic acids, were found to be inactive. An attempt was made to establish a quantitative structure-activity relationship (QSAR) from our experimental data using literature or calculated values for the logarithmic n-octanol/water partition coefficients of the compounds, molar refractivity and sigma values of substituents as well as structural indicator variables. The equations found have moderate predictive power and must be considered as a first step in the investigation of factors determining the biological activity of salicylates, benzoates and phenols.
Elimination from the circulation of cats of 6-keto-prostaglandin E1 compared with prostaglandins E2 and I2
Authors: Förstermann Ulrich , Neufang Brigitte 
Published: April 2011

Abstract
6-keto-PGE1, when injected intravenously (i.v.) or into the aortic arch of cats, produced similar dose-dependent decreases in mean arterial blood pressure. The hypotensive effect of PGI2 was slightly less pronounced compared with that of 6-keto-PGE1, but was equally potent after i.v. and intra-arterial administration. PGE2 had a more potent depressor effect than the two other compounds when injected into the aortic arch, but was much less effective after i.v. injection. Plasma concentrations of 6-keto-PGE1, 6-keto-PGF1α and PGE2 were measured by radioimmunoassay after bolus injections of 6-keto-PGE1, PGI2 and PGE2. The half-life (t 1/2) of the initial rapid decrease in immunoreactivity, indicating the rate of elimination, was found to be 1˙04-2˙19 min for 6-keto-PGE1, 1˙16-2˙01 min for PGI2 and 0˙29-1˙08 min for PGE2. We have confirmed in the cat that 6-keto-PGE1, like PGI2 but unlike PGE2, is not substantially inactivated by the lungs and thus could act as a circulating hormone. However, despite its higher chemical stability, the t 1/2 of 6-keto-PGE1 in the circulation is similar to that of PGI2. PGE2 has a shorter t 1/2, probably due to its extensive pulmonary inactivation. Thus 6-keto-PGE1 seems to be removed from circulation as quickly as PGI2 by organs other than the lung and is unlikely to mediate prolonged effects of PGI2 in the systemic circulation.
The involvement of 5-hydroxytryptamine in the release of dendritic dopamine from slices of rat substantia nigra
Authors: Williams John , Davies John A 
Published: April 2011

Abstract
[3H]dopamine (DA) accumulated by slices of rat substantia nigra was released following superfusion with Krebs solution containing 5-hydroxytryptamine (5-HT) in a dose-dependent fashion with maximal release being produced by 1 × 104 m. This 5-HT-induced release of [3H]DA was calcium-dependent and was inhibited by pretreatment with the 5-HT antagonist cinanserin. These results are interpreted as supporting the possibility that 5-HT has a role in regulating dopaminergic activity in the nigro-striatal pathway.
Models of hepatic drug clearance: discrimination between the ‘well stirred’ and ‘parallel-tube’ models
Authors: Ahmad Anis B , Bennett Peter N , Rowland Malcolm 
Published: April 2011

Abstract
The predictive ability of two models of hepatic drug clearance are compared. The ‘parallel-tube’ model predicts that the steady-state drug concentration following constant rate oral administration increases with increase in hepatic blood flow. The ‘well-stirred’ model predicts that this parameter is not sensitive to changes in hepatic blood flow. Using the steady-state reservoir drug concentration as the discriminatory index, the predictions of the models were tested in a recirculating isolated perfused rat liver system with lignocaine and pethidine, both of which are highly extracted, as test drugs. The steady-state reservoir concentration of both drugs was found to be constant when flow through the liver was increased from 10 ml min−1 to 15 ml min−1. The experimental findings indicate that the ‘well-stirred’ model more accurately describes the elimination of highly cleared drugs with perturbations of flow than does the ‘parallel-tube’ model.
Aminoalkylindoles: atypical dopamine antagonists
Authors: Costall B , Dannenburg W N , Johnson D N , Naylor R J 
Published: April 2011

Abstract
The neuropharmacological profile of a series of aminoalkylindole compounds (AHR-1229-(3-[2-(3-indolyl)-ethyl]-butylamino-1-phenyl-pyrrolidine), AHR1771-(1-[2-(2-methyl-3-indolyl)ethyl]-4-phenyl-3,4-dehydropiperidine), AHR1806-(1-[2-(5-chloro-3-indolyl)-ethyl]-4-phenyl-3,4-dehydropiperidine), AHR1858-(1-[2-(3-indolyl)ethyl]-4-(4-fluorophenyl)-1,2,3,6-tetrahydropyridine), AHR1859-(1-[2-(1-methyl-3-indolyl)ethyl]-4-phenyl-1,2,3,6-tetrahydropyridine), AHR1709-(1-[2-(3-indolyl)ethyl]-4-phenyl-1,2,3,6-tetrahydropyridine) was determined in comparison with the classical neuroleptic agents haloperidol and oxypertine, the latter being of similar indole structure. The indole analogues were shown to antagonize amphetamine-induced toxicity in aggregated mice, to indicate a ‘tranquillizing’ action but, in contrast to haloperidol and oxypertine, showed weak or no activity in other classical behavioural tests for neuroleptic action, catalepsy induction and stereotypy antagonism. In further contrast to haloperidol or oxypertine, the indole derivatives failed to displace [3H]spiperone in radioligand binding assays and failed to increase prolactin levels. However, similarly to both typical and atypical neuroleptic agents, the indole derivatives were shown to inhibit the behavioural hyperactivity resulting from the intracerebral administration of dopamine into the mesolimbic nucleus accumbens of rat. The dissociation of an ability to antagonize a dopamine action in the mesolimbic system from classical neuroleptic actions involving other cerebral dopamine systems is the most important finding of the present study.
The effect of dosator nozzle wall texture on capsule filling with the mG2 simulator
Authors: Jolliffe I G , Newton J M 
Published: April 2011

Abstract
The effect on capsule filling, using an mG2 simulator, of the surface texture of the bore of the dosator nozzle has been investigated for size fractions of lactose. Since the angle of powder-wall friction between the powder and the nozzle cannot be readily measured insitu, this was determined using flat plates with similar surface textures fitted into a Jenike shear cell apparatus. The problems of reproducing surface textures on both types of surface are discussed and a lapping process employed as the most suitable method. Angles of wall friction for the nozzle surfaces were extrapolated from the values obtained from flat plates of similar roughness. Capsule filling experiments, using the mG2 simulator, showed the three resurfaced nozzles produced more uniform fill weights with smaller measured compression and ejection stresses than an untreated nozzle surface. One lapped nozzle surface produced a slightly greater improvement than the others. This supports the concept of an optimum angle of wall friction for powder retention (and hence uniformity of fill) with a minimum of applied compression stress.
Tensile strength requirements for sutures
Authors: Lee S , Hailey D M , Lea A R 
Published: April 2011

Abstract
The official requirements for sutures in Australia are those of British Pharmacopoeia (B.P.). The results of a survey conducted by this Laboratory indicate that the B.P. test and specifications for knot pull strength are no longer appropriate for sutures currently available in this country. It is suggested that tensile strength measurements on sutures should be carried out, without prior soaking, using the load cell type of constant rate of extension apparatus rather than the pendulum type tester specified in the B.P. Use of a simple knot is suitable for testing synthetic sutures, but the surgeon’s knot is preferred for catgut. All products tested easily met both the B.P. and the United States Pharmacopeia (U.S.P.) requirements for tensile strength.