Sustained-release hydrophilic matrix tablets of zileuton: formulation and in vitro/in vivo studies

Abstract

Zileuton is a new active 5-lipoxygenase inhibitor which has been shown to be clinically effective in the treatment of asthma. It is a racemic mixture of S- and R-enantiomers. In the present study, hydrophilic polymer matrix tablets were used for oral controlled delivery of zileuton. The prototype formulations with drug loading of 50–60% were prepared and tested in vitro using USP apparatus I, II and III. In vivo absorption of three formulations with differing release rates was evaluated using crossover designs in beagle dogs. Plasma concentrations of the two enantiomers of zileuton were analyzed by a chiral HPLC method. The results indicated that the release of zileuton from the matrix tablets followed apparent zero-order kinetics when tested using USP apparatus I and II. Prolonged absorption of zileuton was achieved using the hydrophilic matrix system. In vivo drug release estimated by deconvolution based on the data of both S- and R-enantiomers was correlated with in vitro release. Linear relationships between in vitro and in vivo release were obtained with more rapid in vivo release than in vitro.