Is silicified wet-granulated microcrystalline cellulose better than original wet-granulated microcrystalline cellulose?

The purpose of this study was to investigate the effect of granulating water level on the physical-mechanical properties of microcrystalline cellulose (MCC) and silicified microcrystalline cellulose (SMCC). Granulations containing either MCC or SMCC were manufactured at different water levels using a high-shear mixer and were then tray-dried. The water level ranged from 0 to 100%. The granules were evaluated for size, granular and true density, porosity, flow, compactibility, compressibility, and strain-rate sensitivity index (SRS). Increasing the water level affected the size, increased the granular density and flow properties of the granules, and decreased the porosity and compactibility. The compactibilities for both materials were similar and acceptable at each granulating water level up to 40%. They both showed poor compactibility at higher water levels. Yield values and SRSs revealed that MCC and SMCC have similar compressibility, and that both exhibit a plastic component to the deformation process. The granulating water level had no statistically significant effect on the compressibility or the SRS for MCC or SMCC. SMCC did not offer practical advantages over MCC, other than better flow in the powder form, which could be attributed to slightly larger particle size and the presence of silicon dioxide in its structure.

Virus passage through track-etch membranes modified by salinity and a nonionic surfactant.

Why do viruses sometimes not pass through larger pores in track-etch filters? Increasing the salinity (0.8 to 160 mM Na+) decreased phiX174 and PRD1 passage through track-etch polycarbonate membranes (sodium dodecyl sulfate coated but not polyvinylpyrrolidone coated) and PRD1 passage through polyester membranes. Undiminished passage when 0.1% Tween 80 was added implied that nonionic virus adsorption occurred and indicated that high levels of salinity decreased virus passage by decreasing electrostatic repulsion that prevented adsorption.

Intestinal absorption of captopril and two thioester analogs in rats and dogs.

The objectives of this study were (i) to determine whether the reduced absorption of captopril from the colon of humans also occurs in rats and (ii), after confirmation of the relevance of a new rat model, to evaluate the intestinal absorption of captopril and several of its analogs. A model was developed and validated in which specific sites within the GI tract of rats were surgically implanted with a cannula such that animals could be dosed while conscious and unrestrained. The absorption of captopril after administration into the lower GI tract of rats was significantly reduced relative to the upper GI tract, which was consistent with results reported previously in humans. In rats, the absorption of the S-benzoyl thioester prodrug of captopril (SQ-25868) from the lower GI tract was substantially greater than that of captopril. However, the absorption of the S-benzoyl thioester prodrug of 4-phenyl thio-captopril (SQ-26991) from the lower GI tract was only marginally better than that of captopril. In additional studies in dogs, a 12h controlled-release formulation of SQ-25868 provided sustained blood levels of captopril while maintaining acceptable bioavailability (> 80%). Two approaches were tried, without success, to stabilize captopril in vivo: (i) complexation with zinc (SQ-26284) and (ii) use of ascorbic-acid-buffered (pH 3.5) vehicle. The zinc complex might have failed because it has very low solubility, whereas the pH-3.5-buffered vehicle was quickly neutralized within the colonic lumen in rats, and did not stabilize captopril against oxidation. Rapid neutralization might explain why the colonic bioavailability of captopril was not substantially increased when this pH-3.5-buffered vehicle was tried in humans.