Dale D. Maness

Kinetics and mechanism of hydrolysis of furosemide

Abstract Furosemide, a potent diuretic, has been found to give a low bioavailability profile when administered orally which potentially could be due to hydrolysis of the drug prior to absorption. An in vitro kinetic study was performed to elucidate the kinetics and hydrolysis mechanism of furosemide as a function of pH and temperature. In the acidic pH region, below the reported pKa of 3.8, the log K-pH profile indicated specific hydrogen ion catalysis on the undissociated species. In the basis pH region, furosemide hydrolysis is extremely slow. Using the Arrhenius parameters obtained from the studies, furosemide would have a half-life of 178 min under physiological conditions in the stomach of pH 1.0 and temperature of 37°C.

The Influence of Various Dispersion Methods on the Rate of Dissolution of Sulfabenzamide

AbstractThe solvent and melt methods were employed to prepare solid dispersions with various water soluble carriers and a slightly soluble drug, sulfabenzamide. The carriers investigated included citric acid, succinic acid, dextrose, polyethylene glycol 6000, mannitol and urea. Dispersions with dextrose were superior to other carriers in releasing the drug into solution. Melts with both dextrose and urea produced faster rates of dissolution of sulfabenzamide than the coprecipitates from the solvent method. With mannitol and polyethylene glycol 6000, the coprecipitates produced a faster rate of dissolution of the drug than the melt dispersions.

Analysis of erythromycin: I. A study of erythromycin-acid dye complexes

Abstract Erythromycin forms association complexes with four sulfonic acid dyes that can be extracted into chloroform and quantified by spectrophotometry. Of the dyes studied, MO and O IV form 1:1 complexes with the conjugate acid of erythromycin. Solutions containing 20 to 100 μg/ml of erythromycin can be conveniently analyzed by use of MO and the method described.

Analysis of erythromycin: III. Determination of erythromycin by ion-pair extraction with [35S]methyl orange

Abstract A sensitive procedure has been developed for analysis of solutions of the macrolide antibiotic, erythromycin. The method is based on ion-pair formation of the conjugate acid of the drug with an 35 S-labeled isostere of methyl orange, partitioning into chloroform and measurement by liquid scintillation spectrometry. Acceptable accuracy and precision are achieved with the devised technique for solutions of erythromycin in the concentration range of 1 to 10 μg/ml.

Analysis of Erythromycin II. Determination of Erythromycin in Human Blood Serum by Competitive Displacement of [14C]-Erythromycin from E. Coli Ribosomes

Abstract A sensitive and selective method for the determination of erythromycin in human blood serum, in the range of 0.1 to 1.0 μg/ml, is described. The procedure is based on extraction of drug into ether and competitive displacement of [14C]-erythromycin from E. coli ribosomes. The method provides accurate, precise and rapid analyses and should be readily adaptable to bioavailability studies with erythromycin and its salts in man.