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Biomedical subjects

D J Grant

Publications and source records attributed to D J Grant.

14 recordsLinked to original sources

The release of a model low-dose drug (riboflavine) from hard gelatin capsule formulations.

The in vitro release of a model low dose drug, riboflavine, from hard gelatin capsules, formulated with a range of diluents, in the absence and presence of magnesium stearate (0.5, 1.0 and 2.0% w/w), has been assessed by a dissolution technique. Comparison of the values of the time for 50% of the drug content of the capsule to appear in solution T50, by analysis of variance, indicated that the type of diluent significantly influenced the drug release. Irrespective of the magnesium stearate content, the diluents could be ranked in the following order of effectiveness: Primojel greater than sodium bicarbonate greater than Avicel congruent to Dri-flo starch congruent to lactose greater than Emcompress congruent to kaolin greater than starch. Correction of the T50 values for possible adsorption of riboflavine onto the water insoluble diluents, using experimentally determined adsorption isotherms, altered the relative order of effectiveness of the diluents to Primojel greater than sodium bicarbonate greater than kaolin congruent to lactose greater than Avicel congruent to Dri-flo starch greater than Emcompress greater than starch. Comparison of the urinary excretion of riboflavine, after administration of capsule formulations containing lactose, Emcompress or kaolin as the diluent, to volunteers, suggests that the dissolution results not corrected for adsorption provide a better indication of the in vivo performance of the formulations.

Capsules

Effect of solvent flow Reynolds number on dissolution rate of a nondisintegrating solid (potassium chloride).

An apparatus for measuring dissolution rates of solids in the form of disks was designed to possess the following features. The solvent flowed continuously and reproducibly past the disk at various rates associated with calculable Reynolds numbers, Re. The effluent solution was adequately mixed before analysis. The concentration of dissolved solute was much less than the solubility. The surface area of the disk in contact with the solvent was constant during measurements. The dissolution rate of the disk was reproducible, and the disk and its surface could be readily characterized. The apparatus was tested at 37 degrees with compressed potassium chloride and water. The intrinsic dissolution rate, G, was a linear function of Re from Re=360 to greater than 6000. This relationship enabled one unknown constant in each dissolution theory to be expressed in terms of Re. For the diffusion layer model, the thickness of this layer, calculated from the experimental value of G, agreed well with that calculated from the various physical properties, provided that natural convection did not predominate. The dissolution of potassium chloride in this system was, therefore, controlled by diffusion.

Chemistry, Pharmaceutical

Influence of hydrophobic materials on dissolution of a nondisintegrating hydrophilic solid (potassium chloride).

A nondisintegrating hydrophilic solid was covered with coatings of hydrophobic materials as a model to study their influence on dissolution rates. Both solution and sublimation techniques were satisfactory for producing coatings of stearic acid. Only a sublimation method was applicable to magnesium stearate, but the resulting coating consisted mainly of a pyrolysis product, stearone. Reductions in dissolution rates in a continuous-flow system could best be interpreted by assuming that they reflected changes in the area of the hydrophilic solid exposed to the solvent. This concept is based on the assumptions that the intrinsic dissolution rate of uncoated potassium chloride did not change and that no dissolution occurred from coated areas. The most important factors controlling the dissolution rate were the strength of attachment of the hydrophobic coat to the surface of the hydrophilic substrate and the thickness of the coat.

Ketones

Degradation of quinoline by a soil bacterium.

From garden soil a bacterium was isolated which grew aerobically in mineral salts medium with quinoline as sole C source and NH4+ as N source. During growth with quinoline, 2-hydroxyquinoline accumulated in the culture fluid and later disappeared. Whole cells oxidized 2-hydroxyquinoline, 2,6-dihydroxyquinoline and 2,7,8,-trihydroxyquinoline as rapidly as quinoline and without a lag. Catechol was oxidized more slowly by meta-cleavage but at an increasing rate indicative of adaptation. A number of derivatives of benzene and pyridine were not attacked. Whole cells oxidized 2,7,8,-trihydroxyquinoline to a yellow meta-cleavage product which was not further degraded. The following pathway is proposed: quinoline leads to 2-hydroxyquinoline leads to 2,6-dihydroxyquinoline leads to a trihydroxyquinoline (probably not the 2,7,8-compound, but possibly the 2,5,6-compound).

Biodegradation, Environmental