Time-controlled release pseudoephedrine tablets: bioavailability and in vitro/in vivo correlations

In chronopharmacotherapy, circadian changes in disease symptoms are taken i nto account. Press-coated, time-controlled release tablets containing pseud oephedrine hydrochloride as a model drug have been formulated and the suita bility of this highly soluble drug in relation to the new drug delivery sys tem was evaluated. Hydroxypropylmethylcellulose was used in the coat of the tablet to adjust drug release. If such a formulation was administered in t he evening it would have maximal effect in the early morning, and would be useful for the treatment of nocturnal symptoms. Two cross-over, single-dose bioavailability studies were carried out on eight healthy volunteers. A di ssolution test method was developed to establish level A and level C in vit ro/in vivo correlation for four formulations. With a low viscosity grade of polymer, peak concentrations were achieved after five hours. The drug was absorbed much more slowly from tablets containing a high viscosity grade po lymer, with a plasma peak at ten hours. For further development of the drug delivery system described, a dissolution test method at pH 7.2 at a rotati on speed of 150 min(-1) is recommended on the basis of level A in vitro/in vivo correlation.