Bioavailability of sulfonamide suspensions I: Dissolution profiles of sulfamethizole using paddle method.

A comparative bioavailability study was performed using two commercially available, chemically equivalent brands of sulfamethizole suspension. One gram of each suspension was administered to 12 different subjects following a completely randomized crossover design. Serum levels and derived pharmacokinetic parameters were compared statistically. There were no significant differences in the extent of sulfamethizole absorption from the two suspensions as evidenced by the area under the serum level--time curves. Significant differences (p less than 0.05) in the mean serum levels at 0.5 and 0.75 hr and differences in Cmax and tmax indicated that the absorption rate differed for the two products. In vitro tests including particle-size analysis and dissolution studies were performed. The size--frequency distribution of particles in the suspensions was studied using a resistance particle counter. The dissolution characteristics of the two products were studied using the Food and Drug Administration's paddle method and the spin-filter apparatus. Suspension A had a significantly greater amount of drug dissolved at 15 and 30 min using either method. It also had a greater percentage of particles at the smaller size range, indicating that the greater dissolution rate may be related directly to the decreased particle size. A comparison of the in vivo and in vitro results demonstrated a definite rank-order correlation between the dissolution performance of the two suspensions and the in vivo parameters reflecting the absorption rate. Suspension A had a greater amount of drug dissolved at 15 and 30 min and resulted in higher serum levels at 0.5 and 0.75 hr, a higher Cmax, and a shorter tmax.

Correlation of quinidine absorption with disintegration and dissolution rates.

The dissolution profiles of four commercial quinidine sulfate tablets were determined using the USP rotating-basked dissolution apparatus. Substantial differences in dissolution half-times were noted and compared to previously reported disintegration times, absorption rate constants, and times of appearance of peak serum concentrations. Rank-order correlations were observed among all combinations of in vivo and in vitro parameters, indicating that the absorption rates of these tablets are controlled by both disintegration and dissolution.

Simple high-pressure liquid chromatographic determination of trisulfapyrimidines in human serum.

A simple and rapid high-pressure liquid chromatographic method was developed for the determination of sulfadiazine, sulfamerazine, and sulfamethazine in human serum. After the trichloroacetic acid precipitation of the serum proteins, an aliquot of the supernate is injected into a high-pressure liquid chromatograph equipped with a reversed-phase microparticulate column and a fixed wavelength UV detector. For each of the three components of trisulfapyrimidines, a linear calibration curve was observed in the 1-30-microgram/ml range, with the precision of the assay estimated to be +/- 2% (RSD). Preliminary pharmacokinetic data are also presented.

Comparative bioavaiability of four commercial quinidine sulfate tablets.

A comparative bioavailability study was performed using four commercially available, chemically equivalent brands of quinidine sulfate tablets. Two 200-mg tablets were administered to 11 different subjects following a completely randomized crossover design. Serum levels, urinary excretion data, and derived pharmacokinetic parameters were compared statistically. There were no statistical differences in the extent of quinidine absorption from the four brands of tablets as evidenced by the cumulative urinary excretion values and the areas under the serum level-time curves. Significant differences in the mean serum levels at 0.5 and 1 hr and differences in the peak times and absorption rate constants indicate that there was a difference in the absorption rate between Treatments A and D and C and D. A significant difference in the peak times also was noted for Treatments B and C. When mean disintegration times for the four tablet formulations were compared with their values for ka, tmax and mean serum levels at 0.5 and 1 hr, rank-order correlations were observed. A considerable degree of variability in quinidine elimination was noted, with half-life values ranging from 2.71 to 8.12 hr (mean half-life of 5.36 hr).