Interaction of digoxin and montmorillonite: mechanism of adsorption and degradation.

IR, X-ray diffraction, and absorption studies showed that digoxin is adsorbed onto montmorillonite by a reversible adsorption mechanism at pH 2 and 6. Degradation studies indicated abnormally high acid hydrolysis rates for digoxin interacted with montmorillonite. Accelerated digoxin degradation is attributed to the ability of the clay surface to concentrate both digoxin and protons. The effective pH at the clay surface appeared to be 1.5 pH unites lower than the bulk suspension pH. Bisdigoxigenin was the major adsorbed degradation product. A similar catalytic effect also may occur with other neutral drugs that degrade by acid hydrolysis and should be considered in the formulation of clay-containing drug products or their coadministration with other drugs.

Mechanism of adsorption of clindamycin and tetracycline by montmorillonite.

IR and X-ray analyses of the interaction of clindamycin with montmorillonite indicate that clindamycin is adsorbed by a cation-exchange mechanism under pH conditions favoring the cationic form of the drug and by physical adsorption when the unionized drug is present. This physical adsorption is relatively weak since the drug is readily desorbed by alkaline washing. Tetracycline is adsorbed by cation exchange at low pH values where the +00 species predominates. Complexation with divalent interlayer cations contributes significantly to adsorption at higher pH values where the +-0 and +-- species exist. In a strongly alkaline solution, the 0-- species was not adsorbed in the interlayer space of montmorillonite but rather produced an external calcium-tetracycline complex. This study illustrates the utility of X-ray and IR analyses in elucidating the mechanisms responsible for clay-drug interactions.

Microbiological turbidimetric analysis of low chlortetracycline concentrations in feeds.

Recovery studies in which chlortetracycline hydrochloride (CTC-HCI) standard was added to cattle and swine feed supplements at 4.09-9.99 g/ton showed lower antibiotic recovery turbidimetrically (80.6-98.7%) than by the AOAC modified standard as in 38.179(d) (91.2-98.7%) and the plain buffer as in 38.179(b) (93.8-133.0%) methods. Three feeds fortified with a commercial premix at the levels of 5.0 and 10.0 g CTC-HCI/ton showed an overall CTC-HCI recovery of 87.6-110.6% by manual turbidimetric assay. Results were 89.1-108.7% by the AOAC inactivated feed diluent standard and 95.4-125.4% by the plain buffer methods. For some sample extracts (as in cattle feed) the use of heat to stop bacterial growth in the turbidimetric method caused formation of a precipitate. Cooling of cultures to room temperature and rapid reading of sample turbidity followed by standard curve concentrations minimized this interference. The manual turbidimetric assay of low levels of CTC-HCI in feeds appears to offer advantages over other methods.