Development and evaluation of glyburide fast dissolving tablets using solid dispersion technique.

Glyburide is a poorly water-soluble oral hypoglycemic agent, with problems of variable bioavailability and bio-inequivalence related to its poor water-solubility. This work investigated the possibility of developing glyburide tablets, allowing fast, reproducible, and complete drug dissolution, by using drug solid dispersion in polyethylene glycol. Phase-solubility studies were performed to investigate the drug-carrier interactions in solution, whereas differential scanning calorimetry, X-ray powder diffraction, and infrared spectroscopy were used to characterize the solid state of solid dispersions. The effects of several variables related to both solid dispersion preparation (cofusion or coevaporation technique, drug-to-carrier ratio, polyethylene glycol molecular weight) and tablet production (direct compression or previous wet-granulation, tablet hardness, drug, and solid dispersion particle size) on drug dissolution behavior were investigated. Tablets obtained by direct compression, with a hardness of 7-9 Kp, and containing larger sized solid dispersions (20-35 mesh, i.e., 850-500 microm) of micronized glyburide in polyethylene glycol 6000 prepared by the cofusion method gave the best results, with a 135% increase in drug dissolution efficiency at 60 min in comparison with a reference tablet formulation containing the pure micronized drug. Moreover, the glyburide dissolution profile from the newly developed tablets was clearly better than those from various commercial tablets at the same drug dosage.

Three-dimensional magneto-optic trap for micro-object manipulation.

A magneto-optic trap for micro-objects is described. Magnetic beads were trapped by optical tweezers while being rotated by a new integrated magnetic manipulator. Rotation was achieved with eight electromagnets with tip-pole geometry. The time orbital potential technique was used to achieve rotation of magnetic beads. Trapping in three dimensions and rotation of magnetic beads on three axes are demonstrated with forces up to 230 pN and force momenta of up to 10(-16)N m . A position-detection apparatus based on an interferometric scheme provides nanometer sensitivities in a few milliseconds.

Efficacy and safety of mangafodipir trisodium (MnDPDP) injection for hepatic MRI in adults: results of the U.S. Multicenter phase III clinical trials. Efficacy of early imaging.

The efficacy of contrast-enhanced magnetic resonance imaging (MRI) for detecting and characterizing, or excluding, hepatic masses was assessed in 404 patients, following the intravenous administration of mangafodipir trisodium (MnDPDP) injection, a hepatic MRI contrast agent. An initial contrast-enhanced computed tomography (CT) examination was followed by unenhanced MRI, injection of MnDPDP (5 micromol/kg IV), and enhanced MRI at 15 minutes post injection. Agreement of the radiologic diagnoses with the patients' final diagnoses was higher for enhanced MRI and for the combined unenhanced and enhanced MRI evaluations than for unenhanced MRI alone or enhanced CT using the clinical diagnosis as the gold standard. Mangafodipir-enhanced MRI uniquely provided additional diagnostic information in 48% of the patients, and patient management was consequently altered in 6% of the patients. MnDPDP-enhanced MRI was comparable or superior to unenhanced MRI and enhanced CT for the detection, classification, and diagnosis of focal liver lesions in patients with known or suspected focal liver disease.

Study on the absorption of ketoprofen topically administered in man: comparison between tissue and plasma levels.

In this study the transcutaneous passage of ketoprofen (gel) topically administered and its distribution in the inner part of the knee-joint were evaluated in six patients. The ketoprofen concentrations detected were: 4.70 mcg/g +/- 3.87 in the intra-articular adipose tissue; 2.35 mcg/g +/- 2.41 in the capsular sample and 1.31 mcg/g +/- 0.89 in the synovial fluid. Plasma concentrations of the drug were also examined. In the samples studied, the ketoprofen levels amounted to about one hundred times higher than the plasma concentrations.

Plasma and synovial fluid concentrations of isoxicam in meniscectomized patients.

Concentrations of isoxicam in the plasma and synovial fluid of 7 patients were investigated by means of high-pressure liquid chromatography. The samples were collected after 7 days' treatment with a single 200 mg isoxicam capsule taken each morning. A highly significant correlation was found (r = 0.82; p less than 0.05) between isoxicam concentrations in the plasma and in the synovial fluid. The mean concentration (+/- s.d.) was 25.54 +/- 10.91 micrograms/ml in the plasma and 17.47 +/- 6.54 micrograms/ml in the synovial fluid; the ratio between isoxicam concentrations in the synovial fluid and in the plasma was 71.06% +/- 18.83.

Quantitative high-performance liquid chromatographic determination of delta 4-3-ketosteroids in adrenocortical extracts.

A high-performance liquid chromatographic method is described for the determination of seven steroids in adrenocortical extracts showing a delta 4-3-ketonic conjugated system. The seven steroids (cortisol, cortisone, 11-dehydrocorticosterone, corticosterone, 11-deoxycortisol, aldosterone and 11-deoxycorticosterone) were separated with a chloroform-methanol gradient on a 5-micron silica column and with a water-acetonitrile gradient on a 10-micron RP-8 column. Effluents were monitored by UV absorption at 242 nm. Quantitative analysis was performed by comparing peak areas, which are proportional to the amounts of the individual substances (external standard method). The method is rapid, sensitive, easy to perform and reproducible.

Determination of ketoprofen by direct injection of deproteinized body fluids into a high-pressure liquid chromatographic system.

A rapid, sensitive, and specific determination of ketoprofen in human and animal deproteinized body fluids by reversed-phase high-pressure liquid chromatography is presented. The acid is detectable in amounts as low as 0.1 microgram/ml. Limits of error are in the range of +/- 5.1% of the sample mean.

New and simple method for determination of 2-(3-benzoylphenyl)propionic acid in body fluid.

A simple, fast, sensitive, and reliable method for the determination of 2-(3-benzoylphenyl)propionic acid in biological fluid is described. The method is based on a quantitative ether extraction of plasma samples followed by TLC separation, spot visualization and elution, and determination at 255 nm. The acid is detectable in amounts as low as 1 mug.