Design and evaluation of sustained-release tablets of lithium in a fat matrix and its bioavailability in humans

The development of sustained-release lithium (Li) tablets, intended to release the active principle at a rate of 1.0 mM/h for 10 h, was undertaken. The parameters used for the control of the release were the glyceril palmite-stearate content, the carboxypolymethylene content, and the compression force. The experimental design is based on Hadamard's matrices and is of the adaption by stages type. The formulation seen as optimal from in vitro assays was later assessed in vivo by a crossover study of six subjects. The parameters used to measure the bioavailability were the total amount of Li excreted in the urine in the 96 h following ingestion, the maximum urinary excretion rate, and the time at which this rate was reached. The acceptability interval for the first two parameters was established from the theoretical curve of urinary excretion, which was calculated by convolution of the desired in vivo release variable (1.0 mM/h for 10 h) by the absorption-disposition variable obtained after administering the preparation in Li carbonate capsules. The results obtained show that the bioavailability of the formulation is 75% of the immediate-release formulation used as control and that the release rate, although close to the desired value, lasts only 7 or 8 h; these results agree with those given by numerical deconvolution using the mean urinary excretion curves.