SUSTAINED-RELEASE HYDROPHILIC MATRIX TABLETS OF ZILEUTON - FORMULATION AND IN-VITRO IN-VIVO STUDIES

Zileuton is a new active 5-lipoxygenase inhibitor which has been shown to be clinically effective in the treatment of asthma. It is a racemi c mixture of S- and R-enantiomers. In the present study, hydrophilic p olymer matrix tablets were used for oral controlled delivery of zileut on. The prototype formulations with drug loading of 50-60% were prepar ed and tested in vitro using USP apparatus I, II and III. In vivo abso rption of three formulations with differing release rates was evaluate d using crossover designs in beagle dogs. Plasma concentrations of the two enantiomers of zileuton were analyzed by a chiral HPLC method. Th e results indicated that the release of zileuton from the matrix table ts followed apparent zero-order kinetics when tested using USP apparat us I and II. Prolonged absorption of zileuton was achieved using the h ydrophilic matrix system. In vivo drug release estimated by deconvolut ion based on the data of both S- and R-enantiomers was correlated with in vitro release. Linear relationships between in vitro and in vivo r elease were obtained with more rapid in vivo release than in vitro.