Cefazaflur: kinetics of hydrolysis in aqueous solution, acid dissociation constant and alkaline decomposition to fluorescent products.

The values of the pseudo-first order hydrolysis rate constants in the pH range 1 to 10, and the pKa, were determined for cefazaflur in aqueous solution at 37 degrees C and ionic strength 0.2 M. A fluorimetric assay, based on alkaline hydrolysis at 100 degrees C, was also developed for this compound. The results are consistent with previously reported related properties of other monoprotic cephalosporins.

The influence of polyvinylpyrrolidone on the solution and bioavailability of hydrochlorothiazide.

The dissolution properties of hydrochlorothiazide-PVP 10 000 mechanical mix and coprecipitate systems were qualitatively similar to those previously reported using hydroflumethiazide. Quantitative differences were dependent on the proportion of PVP present, its molecular weight and method of incorporation. Cumulative urinary excretion data from test capsule preparations showed that bioavailability was enhanced by the presence of PVP. However, the degree of enhancement was less than that expected from constant surface area disc rate studies. Dissolution tests on the capsule formulations, using the U.S.P. basket stirrer assembly, did not correlate with in vivo results. Using the Levy beaker method and a stirring speed of 40 rev min-1, good correlation between amount dissolved in 30 min and amount excreted in urine after 24 h was obtained. The dissolution tests revealed that PVP retards the initial dissolution from capsule dosage forms, probably by retarding deaggregation and dispersion of drug particles.

The influence of polyvinylpyrrolidone on the dissolution properties of hydroflumethiazide.

The incorporation of hydroflumethiazide with polyvinylpyrrolidone (PVP) was found to retard and to enhance the dissolution of the drug from compressed discs, the magnitude of the effect being dependent on the proportion of PVP present and its method of incorporation. The most active system dissolved sixteen times faster than pure hydroflumethiazide. Low concentrations of PVP were also found to decrease the apparent solubility of hydroflumethiazide while at high concentrations solubility was enhanced. X-ray and infrared analysis of systems suggested the presence of an amorphous form of hydroflumethiazide in coprecipitate systems. The dissolution data were consistent with a physical model which takes account of the roles played by crystalline and amorphous hydroflumethiazide together with the complexing and crystal growth inhibiting effect of PVP on hydroflumethiazide.

Resistance of Bacillus subtilis spores to inactivation by gamma irradiation and heating in the presence of a bactericide. 3. Factors affecting rates of inactivation by phenylmercuric nitrate.

Aqueous suspensions of Bacillus subtilis NCTC 8236 spores, surviving gamma irradiation from a cesium-137 source, exhibited an enhanced rate of inactivation compared to nonirradiated spores when heated with 0.04% phenylmercuric nitrate. The enhanced rate of inactivation, observable from survival curves, was noted when spores were irradiated with 150,000 rad under air in either the presence or absence of the bactericide. The magnitude of the enhanced inactivation rate increased as the irradiation dose under air increased from 150,000 to 300,000 rad. The inactivation rates of spores surviving irradiation with 150,000 rad under either oxic or anoxic conditions did not exhibit a simple quantitative relationship. The enhancement effect was observed when the severity of the heat treatment was increased by either reducing the pH from 8 to 6 or raising the temperature from 70 to 90 C.

Resistance of Bacillus subtilis spores to inactivation by gamma irradiation and heating in the presence of a bactericide. I. Suitability of viable count procedures.

A statistical evaluation of viable count procedures utilized for obtaining treatment survival curve data for Bacillus subtilis NCTC 8236 spores is described. Within the various recovery conditions tested, incubation on nutrient agar containing 1% dextrose for 48 hr at 37 C was found to promote the highest count of viable spores surviving a variety of bactericidal treatments involving gamma irradiation, heat, and chlorocresol. The count of viable spores on the medium was not significantly altered when the dextrose was added to the nutrient agar either before autoclaving or aseptically at 50 to 55 C from a solution sterilized by filtration. The volume of medium which promoted the highest count of viable spores was 20 ml per 85 mm of diameter in disposable plastic plates. Counts of viable spores were reproducible on successive batches of media. The carry-over of variable concentrations of chlorocresol into the medium from serial dilutions affected the count of viable spores. Spores in the aqueous stock suspension used for all experiments were uniformly distributed after shaking and did not diminish significantly in viability after 16 months of storage at 5 C. Grouping of indexes of dispersion, calculated from quintuplicate plate colony counts, indicated that the suitability of the viable count procedures, employed for the enumeration of spores surviving the various bactericidal treatments, tended to diminish as the level of spore inactivation exceeded 95%.

Resistance of Bacillus subtilis spores to inactivation by gamma irradiation and heating in the presence of a bactericide. II. Factors affecting rates of inactivation by phenolic bactericides.

Aqueous suspensions of Bacillus subtilis NCTC 8236 spores, surviving 150,000 or 300,000 rad of gamma irradiation under air from a cesium-137 source, exhibited an enhanced rate of inactivation, compared to nonirradiated spores, when heated with different phenolic bactericides. The apparent magnitude of the enhanced inactivation rate, observed from survival curves, increased progressively with the irradiation dose applied and diminished progressively as the severity of heat treatment with 0.2% chlorocresol was increased either by raising the temperature from 70 to 90 C or reducing the pH from 8 to 6. The enhanced inactivation rate was unaffected when the concentration of sodium chloride added to 0.2% chlorocresol was altered from 0.4 to 0.8%. The enhancement effect was also observed when the heat treatment was carried out with 0.5% phenol and 0.3% m-cresol.