PubMed Health⌕ Search

Biomedical subjects

C Graffner

Publications and source records attributed to C Graffner.

16 recordsLinked to original sources
PubMed1992

Investigation of the applicability of a tensile testing machine for measuring mucoadhesive strength.

The applicability of a tensile testing machine (M30K, JJ Lloyd Instruments Ltd, GB) is investigated for measuring mucoadhesive strengths. A sample of an aqueous dispersion of a polymer with expected mucoadhesive properties is placed between two homemade discs of polyoxymethylene. The upper disc is mounted on a movable part of the machine while the lower disc is fixed on the stationary frame. A tensile force is submitted and the maximum detachment force at fracture and the adhesion work are estimated from the force displacement curve recorded. In some experiments, native mucous tissue of the large intestine of pigs was glued to the upper disc. Four polymers polycarbophil (Carbopol EX-55), carboxypolymethylene (Carbopol 934P), hydroxypropylmethylcellulose (Methocel K4M), and sodium alginate, are used in five different concentrations. At least three measurements are made of each polymer and concentration. Viscosity and osmolality are determined. By standardizing the time of sample equilibration and the run rate before measurement, it is possible to get good reproducibility of the tensile values. Based on the maximum nominal breaking force and the work consumed, it is concluded that the tensile strength is dependent both on the concentration and the type of polymer. The conclusions are the same independent of whether mucous pig tissue is used, or not. The same rank order in adhesive properties of the polymers is achieved as from using modified surface tensiometers.

Adhesiveness↗
PubMed1992

Optimization of a matrix tablet formulation using a mixture design.

The simplex centroid design was applied to the optimization of a modified release tablet formulation. A base granulation was made with the active ingredient naftidrofuryl. The variables investigated included fractions of the excipients microcrystalline cellulose, lactose and dicalcium phosphate dihydrate. The release rate, crushing strength, friability and weight variation were determined as response parameters. Mathematical models were fitted to the data obtained by the lattice method, described by Scheffé and by means of multiple linear regression. Regression analysis indicated a relatively good fit of the models. On the basis of the regression models, contour plots were constructed. An increase in the amount of dicalcium phosphate caused lower release rate and increased weight variation. An increase in the content of lactose showed lower strength and increased friability, whereas an increase in the amount of microcrystalline cellulose had the opposite effect.

Chemistry, Pharmaceutical↗
PubMed1990

Plasma concentrations of remoxipride and the gastrointestinal transit of 111In-marked extended-release coated spheres.

To explore the oral absorption of remoxipride, spheres of remoxipride were labeled with indium-111 colloid before coating with a release-controlling ethylcellulose membrane. Since the labeling remained inside the coating, it was suitable as a marker. Eight healthy volunteers were given a single dose of 100 mg remoxipride in 111In-marked spheres as a multiple-unit capsule. The radioactivity and the position of the spheres (microcapsules) were followed externally for 30 hr by gamma scintigraphy. Parallel to this, plasma concentrations were drawn for 48 hr to confirm the extended dissolution and absorption of remoxipride. The hard gelatin, multiple-unit capsule released the microcapsules within the stomach. These were then rapidly emptied into the small intestine, within 0.5-1 hr. There was then an immediate distribution in the upper small intestine before collection in the lower portion, within 2-5 hr. After passing into the large intestine, there was again extended distribution of the microcapsules. A mean Cmax of 2.7 microM remoxipride was achieved 4 hr after drug administration and a mean AUC of 26.1 mumol.L-1.hr was achieved. Judging from the absorption versus time profile, calculated according to the Wagner-Nelson method, and the scintigraphic images, it is concluded that the main absorption occurs from the small intestine. Data from four volunteers, however, indicated a comparatively good absorption also from the large intestine. Due to the good absorption properties, it is reasonable to expect a low variation in the extent of bioavailability of remoxipride after administration in an extended-release, multiple-unit capsule formulation.

Administration, Oral↗
PubMed1989

Comparative dissolution studies of rectal formulations using the Basket, the Paddle and the Flow-Through methods. I. Paracetamol in suppositories and soft gelatin capsules of both hydrophilic and lipophilic types.

The applicabilities of the Paddle, the Basket and the Flow-Through methods have been investigated for seven different rectal compositions of hydrophilic and lipophilic type. The formulations were studied with respect to in vitro dissolution rate and behaviour in the different techniques. It was found that the composition has a considerable influence on the behaviour of the dosage form and this must be taken into account when judging the applicabilities of the three dissolution tests. The Paddle, the Basket and the Flow-Through methods are considered to be equivalent methods for the dissolving suppositories tested. The Flow-Through method is applicable for all the seven compositions tested; however, a low flow rate (8 ml/min) is necessary to use for soft gelatin capsules when both the coefficient of variation and the behaviour of the dosages within the techniques is taken into consideration.

Acetaminophen↗
PubMed1986

Tolerance and pilot pharmacokinetics of amiflamine after increasing single oral doses in healthy subjects.

Oral doses of 1 to 100 mg amiflamine, a new reversible monoamine oxidase type A-selective inhibitor, were given for the first time in humans to six healthy men. No apparent pharmacologic effects were recorded until the 80 mg dose. After 100 mg, one subject developed symptoms indicative of an overdose. Amiflamine is extensively metabolized by two consecutive N-demethylations. The biotransformation patterns in plasma and urine were found to correlate with the debrisoquin metabolic ratio.

Adult↗
PubMed1986

Pressor response of oral tyramine in healthy men given amiflamine and placebo.

During two baseline challenge tests, oral tyramine (50 to 400 mg) was given to 12 healthy men to find each individual's cardiovascular pressor response. All 12 subjects "tolerated" 200 mg oral tyramine, but three of the 12 developed an increment in systolic blood pressure greater than 30 mm Hg when given a dose of 400 mg. Thereafter, amiflamine, 5 mg bid (n = 8), or placebo, 1 capsule twice a day (n = 4), were given in a double-blind fashion for 7 days, and oral tyramine challenge tests (12.5 to 400 mg) were given on days 5 to 7. During dosing with amiflamine or placebo, no subject tolerated 400 mg oral tyramine and no difference between the two regimens was found with regard to tyramine response. Plasma concentrations of amiflamine and two of its metabolites were measured on days 4 to 7. Steady-state concentrations were reached within 4 to 5 days. Plasma concentrations of tyramine after 400 mg tyramine showed a positive correlation with the increase in systolic blood pressure (P less than 0.001).

Administration, Oral↗
PubMed1985

Preformulation studies in a drug development program for tablet formulations.

Recently developed techniques were applied in a preformulation program to select a compound and a suitable salt for use in a one-month toxicological test. The program showed that valuable information can be obtained prior to the choice of a compound as a candidate for a solid-dosage form. Information about the physical and mechanical properties of the chosen compound can be obtained with a limited amount of substance, i.e., surface color and hygroscopicity (1-2 g), dissolution rate and solubility (1-2 g), powder properties (1-2 g), and compaction properties (5-7 g).

Chemical Phenomena↗
PubMed1979

Haemodynamic effects and pharmacokinetics of a new selective beta1-adrenoceptor agonist, prenalterol, and its interaction with metoprolol in man.

The haemodynamic effects of the selective beta1-adrenoceptor agonist prenalterol were studied in healthy subjects before and after therapeutic doses of the selective beta1-adrenoceptor blocker metoprolol. Plasma levels of the drugs were also determined in order to calculate certain pharmacokinetic variables. Intravenous infusion of prenalterol 0.13, 0.25 and 0.50 mg induced a dose-dependent decrease in total electromechanical systole (QA2) and pre-ejection period (PEP). The effect on left ventricular ejection time (LVET) was not significant. Increases in systolic blood pressure and heart rate were dose-dependent. Diastolic blood pressure did not change significantly. When metoprolol had been administered in a cumulative dose of 150 mg (mean maximal plasma level, 284 nmol/l) prenalterol had to be administered in doses that were twelve times higher than before the beta-blocker in order to induce the same haemodynamic effects. Prenalterol was rapidly distributed with an average half life of 8 min. This indicates that distribution equilibrium will be achieved within 30 min after intravenous administration. The overall elimination rate in the post-distributive phase corresponded to an average half life of 2.0 h.

Adrenergic beta-Agonists↗
PubMed1979

Pharmacokinetics of metoclopramide intravenously and orally determined by liquid chromatography.

1 A rapid and sensitive method, based on liquid chromatography, has been developed for determination of metoclopramide concentrations in plasma and urine samples. Concentrations down to 15 nmol/1 (5 ng/ml) of plasma and 100 nmol/1 (30 ng/ml) of urine could be determined with a relative standard deviation of less than or equal to 10%. The method was used to study disposition of metoclopramide in healthy volunteers following single doses intravenously and orally as aqueous solution and a slow release tablet. 2 The initial distribution after intravenous administration was very rapid. The elimination half-life postdistribution was 4.9 h. The apparent volume of distribution, Vd, was 3.0 1/kg body weight. On average 19% was excreted unchanged after intravenous administration of 5 and 10 mg (15 and 30 mumol) of drug. The rate of absorption of metoclopramide was delayed after administration of a slow release tablet and the maximum plasma concentration was about 50% lower than after a solution. The extent of bioavailability was the same following the two different formulations suggesting a first-pass elimination of 25-40%.

Administration, Oral↗
PubMed1975

Pharmacokinetics of procainamide intravenously and orally as conventional and slow-release tablets.

Pharmacokinetics of procainamide were studied in healthy volunteers after single doses intravenously and orally as conventional and slow-release tablets and after repeated oral doses to steady state. The initial distribution after intravenous administration was rapid and the overall elimination in the beta-phase corresponded to t1/2 of 2.7 hr. The mean volume of the central compartment was small and only 4 percent of V-d (beta), which was 2.3 l/kg body weight. About 65 percent was excreted unchanged after intravenous administration and about 55 percent after a single oral dose of 500 mg. The recovery of the metabolite N-acetylprocainamide was 12 percent after both routes of administration. Procainamide was completely absorbed from the gastrointestinal tract and the first-pass elimination was very limited. The rates of absorption from the tablet compositions were well correlated to the in vitro dissolution properties. Administration of slow-release tablets every 8 hr gave about the same mean plasma level at steady state as ordinary tablets given every 4 hr, and the availability was the same from both preparations. The occasional high plasma concentration peaks after ordinary tablets were not observed after the slow-release tablets. Renal clearance was about 500 ml/min, indicating an active secretion in the tubules.

Acetylation↗
PubMed1975

Elimination rate of N-acetylprocainamide after a single intravenous dose of procainamide hydrochloride in man.

Equations were derived which made it possible to determine the elimination rate of N-acetylprocainamide from urinary data after intravenous administration of procainamide hydrochloride. A single dose of 500 mg of the drug was infused intravenously in four healthy subjects. On the basis of theose equations, the formation rate of the metabolite could be calculated presuming that all rate processes were occurring by first-order processes. However, close examination of the excretion rate data appears to support the contention that the formation or excretion of N-acetylprocainamide may be occurring by a saturable process

Acetylation↗
PubMedDate not supplied

Intra- and intersubject variation of erythromycin absorption from single-unit and multiple-unit enteric-coated products.

Based on the in vitro dissolution test for erythromycin capsules introduced in USP XX, Suppl. 3, there are no reasons to expect any difference in bioavailability after administration of two enteric-coated products, tablets and pellets in hard capsules. The present results in vivo are contradictory and, following duplicate administrations of the two preparations to 12 volunteers after a standardized breakfast, it is apparent that the multiple-unit, pellets, produce a better reproducibility in absorption both within and between subjects than the single-unit tablets. All subjects attained measurable levels of erythromycin on all occasions after administration of pellets, while levels were below the detectable limit on six out of the 24 occasions tested after administration of tablets. The better reproducibility of serum levels after pellets than after tablets was also shown in a descriptive way and is given as a low median discrepancy value of 23.5 per cent (moderate) compared to 73.2 per cent (large).

Adult↗