Gastro-intestinal bioavailability assessment of commercialy prepared sustained-release lithium tablets using a deconvolution technique

Abstract

The bioavailability of a commercial formulation of sustained release Lithium, containing 10.4 mM in the form of carbonate per tablet, was evaluated by a bioequivalency assay using 10 healthy volunteers. As reference, gelatine capsules containing the same dosage were used. By numerical deconvolution of the mean urinary excretion curves an equation representing the amounts of Lithium released in the gastrointestinal tract was obtained, proving equal to 1.0 + 0.94.t - 0.012.t, 0 ! t ! 8 hours. This results were confirmed by the Bayesian interpretation of the bioequivalency study, with acceptability intervals determined for each parameter used, total amount of lithium excreted in the urine and maximum urinary excretion rate. The limits were established from the curves obtained under simulation using the absorption-disposition parameters of the urinary excretion curve and optimum gastrointestinal release Kinetics. The results suggest that the bioavailability of the tablets is moderately reduced as the result of the release rate being lower than the optimum value.

The correlation between the amounts dissolved in vitro using the rotating basket at 100 rpm and HC1 0.1 N as solvent and the amounts released in vivo estimated by numerical deconvolution was excelent.