Introduction

Increased complications and expense involved in marketing of new drug entities has focused greater attention on development of sustained and controlled release drug delivery systems [1]. The purpose of the systems is to maintain drug concentration in the blood or in target tissues at a desired value as long as possible. To achieve predictable and reproducible release rates, extended duration of activity for short half-life drugs, decreased toxicity, and reduction of required dose, optimized therapy and better patient compliance, a sustained-release (SR) formulation of various drugs is desirable [2].

Over the years, we have been working on the development of plasma-assisted preparation of multi-layered tablets applicable to oral drug delivery system (DDS) [3-5]. In previous papers, we reported the preparation of SR system by oxygen plasma-irradiation to the double- compressed tablet having a mixture of plasma- crosslinkabe material, like polystyrene (PSt) or hydroxypropyl methylcellulose acetate succinate (HPMCAS), and plasma-degradable material, like polyoxymethylene (POM) or lactose, as a wall material [6,7]. When oxygen plasma was irradiated to the outermost layer of the tablet, plasma-degradable material could be selectively eliminated and simultaneously plasma-cross-linkable material undergoes the rapid crosslink reaction to result in the formation of the porous outer layer of the tablet. As a result, the drugs could be released slowly from the tablet through the resulting micropores.

The objective of this study was to develop once-daily sustained-release dosage forms, which releases drug at zero-order rate with accurate control in the gastrointestinal tract.