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The action of colloidal silicon dioxide as a glidant for lactose, paracetamol, oxytetracycline and their mixtures.

Anomalies are observed in some of the physical and mechanical properties of mixtures of lactose, paracetamol and oxytetracycline when small amounts of colloidal silicon dioxide are added to them. Owing to its differing propensities to coat the particles of the host powders, the silicon dioxide acts as a glidant for the lactose and paracetamol, but as an antiglidant for the oxytetracycline.

Acetaminophen

Effects of amorphous silicon dioxides on drug dissolution.

The dissolution profiles of prednisone, digoxin, and griseofulvin in simulated GI fluids were determined after solvent deposition or ball milling with three commercially available grades of amorphous silicon dioxide. The former procedure resulted in adsorbates showing evidence of drug entrapment by the two grades with larger average pore diameters. Ball milling the drugs with the grade possessing the largest average particle diameter produced triturations with the slowest dissolution rates. A relationship between drug dissolution and extent of dilution with the amorphous silicon dioxides was shown. Particle-size measurements revealed that the ball milling procedure was more apt to broaden the size distribution as compared with the solvent-deposition method of drug incorporation.

Chemistry, Pharmaceutical

Rheological and drug release properties of oil gels containing colloidal silicon dioxide.

The rheological properties of oil gels prepared by dispersing colloidal silica in n-dodecane and 1-dodecanol were examined. The differences in gel strength using these two media were accounted for by the difference in the extent of hydrogen bond formation between the silanol groups on the silica surface. The incorporation of methyl salicylate further modified the rheological properties of the gels. The drug was capable of hydrogen bonding with silanol groups in the n-dodecane gels, which increase gel strength at low concentrations; at high concentrations, the drug acted as a plasticizer. In 1-dodecanol systems, the drug acted solely as a plasticizer. Adsorption studies showed that methyl salicylate was adsorbed only on the silica particles in the n-dodecane medium. Interaction of the drug with the silanol groups in the n-dodecane systems did not appear to effect methyl salicylate release from the gels.

Adsorption

Protein binding to monosodium urate monohydrate, calcium pyrophosphate dihydrate, and silicon dioxide crystals. I. Physical characteristics.

The protein adsorptive properties of monosodium urate monohydrate (MSU), silica (Si), and calcium pyrophosphate dihydrate crystals were studied by qualitative and quantitative techniques. Immunoglobulin G (IgG) was adsorbed preferentially by MSU crystals from normal human serum and demonstrated high-affinity binding isotherms when compared with several isolated proteins in solution. The physical characteristics of this reaction suggest principally an ionic mechanism, since adsorption was enhanced by decreasing pH or ionic strength. Weaker physical forces also were suggested by studies showing enhanced adsorption at lower temperatures. The following order of affinity for Si or MSU crystals was found when equal concentrations of proteins were compared: Cohn fraction II greater than lysozyme greater than beta lactoglobulin greater than bovine serum albumin greater than ovalbumin. IgG adsorption to the crystals studied may explain certain features of their biological activity. It is suggested that this phenomenon blocks the membranolytic properties of crystals and stimulates their phagocytosis through interaction with Fc receptors on the surface of the phagocytic cells.

Adsorption

Determination of porosity and pore-size distribution of aspirin tablets relevant to drug stability.

Total porosity and pore-size distribution of aspirin tablets prepared from aspirin, starch USP, and precipitated colloidal silicon dioxide were determined using mercury porosimetry. The model represented a hydrolyzable drug substance in combination with simple excipients. The role of starch and silicon dioxide on the microstructure of the tablets was investigated, as was the chemical stability of various systems. In general, the porosity of tablets containing a constant quantity of starch increased linearly with silicon dioxide concentration. Examination of the pore-size distribution, however, revealed that a low concentrations silicon dioxide functioned primarily to reduce the size and volume of coarse pores representing the spaces between the agglomerates of starch and aspirin particles. This effect was optimum at 3%. A further increase in silicon dioxide concentration produced tablets with relatively larger pore sizes. Studies of changes in the porosity characteristics of tablets as influenced by water vapor over time showed distinct differences in this complex parameter. A unique trend in the change of the pore-size distribution was noted with tablets containing 3% silicon dioxide. These observations are discussed relative to the stability of aspirin tablets in which this concentration of silicon dioxide produced a maximum stabilizing effect.

Aspirin

A microelectronic pH sensor.

This paper presents preliminary data on a new integrated circuit microelectronic pH sensor. The device is extremely miniaturized by the use of integrated circuit technology, and uses the intrinsic hydrogen ion selective properties of the gate insulator material. In order to make the device compatible with aqueous solution monitoring, the silicon dioxide-silicon nitride gate insulator structure is used. The integrated circuit chip was designed, processed, and packaged by a variety of techniques which protect all metal parts from the aqueous solution. Test data are reported on leakage current, sensitivity, reproducibility, linearity, stability, response time, and life. The results indicate that this type of pH sensor may have many significant advantages for biomedical research and application.

Biomedical Engineering

[Preparation of highly puried pepsin by aminosilichrome chromatography].

The procedure for preparing highly purfied pepsin by chromatography on silicon dioxide with attached aminogroups (aminosilochrome) has been devised. Pepsin is eluated step=by-step: 0.0025 M and 0.05 M HCl. Results of disc-electrophoresis of purified pepsin bive evidence that the resultant preparation contains no admixtures. The activity of purified pepsin is 69 units per mg.

Chromatography, Affinity

Production of a nonwettable enamel surface.

A water-repellent enamel surface was achieved using a new material that is a combination of fumed silicon dioxide and a silane. The effects of this coating on enamel were studied. In vitro studies suggest that the material produces good water and saliva repellency. However, no reduction in bacterial colonization between treated and control enamel occurred. results of in vivo investigations of coated and control Styroflex strips showed a reduction in deposits on the former. Retention with or without previous acid etching of the enamel was poor.

Dental Bonding

Silicate pneumoconiosis of farm workers.

Abnormal numbers of birefringent particles have been found in the lungs of seven patients (five vineyard workers, one farmer, and one rural resident) in association with a spectrum of early to late interstitial inflammation and fibrosis. Nodular granulomas of the type seen in silicosis were absent. Scanning electron microscopy and energy dispersive x-ray analysis of 177 individual particles (less than 5 micrometer.) in situ in the lungs of four of the patients showed mostly silicates (notably aluminum, silicon, and potassium), with 5 to 10 per cent silicon dioxide. An analysis of particles less than 5 micrometer. from both vineyard and non-vineyard soil showed lung and soil particles to have a similar composition. The presence of large amounts of silicates in the lung tissues, in association with chronic inflammation and fibrosis, implicates the silicates in the causation of the fibrosis. The silicate deposits may, in large part, be a marker, reflecting a mixture of toxic soil additives or pesticides found in commercial clay silicate products or in dusts from the soil itself. The findings do not exclude lung pathology of a similar nature in regions outside of the farm.

Aged

Relative thrombogenicity of polydimethylsiloxane and silicone rubber constituents.

Medical grade silicone rubber (MGSR) is composed of polydimethylsiloxane (PDMS) as well as silica filler, oxidation products from the curing process, and other components. In a test that excludes air-blood interfaces, PDMS radiation cured under nitrogen has a whole blood clotting time 22% longer than MGSR. Curing the PDMS under oxidizing conditions maintains a 10% prolongation, but addition of silica filler to the PDMS returns the clotting time to that of MGSR. Extracting MGSR with solvents other than water appreciably lowers the clotting time. These results indicate the "pure" PDMS has an intrinsically high thromboresistance. Thrombogenicity is increased by the use of silica filler and oxidizing cure, as in MGSR.

Biocompatible Materials

In vivo tissue reactivity of radiation-cured silicone rubber implants.

Silicone rubber implants are clinically used in large numbers and elicit a milk tissue reaction. An occasional patient develops an accentuated reaction, an observation which has stimulated clinicians to try to understand this process more fully. The chemistry of medical silicone implants, including quantitative composition, is reviewed. This in vitro laboratory study show less tissue reaction-cured silicone with SiO2 filler. A proposed system for fabrication and curing of a silicone implant, with the qualities of strength and diminished tissue reactivity, is discussed.

Animals