Development and in vitro-in vivo evaluation of a novel sustained-release tablet based on constant-release surface

Subject The release rate of hydrophilic gel tablets varies depending on their surface area. In this study, we aimed to develop a sustained-release tablet that maintains a constant release area during drug release. Methods Initially, commercially accessible gliclazide, sinomenine hydrochloride, and trimetazidine hydrochloride tablets were side coated with ethylcellulose to ensure a constant release area. Next, sustained-release gliclazide tablets were prepared by altering their size and thickness to assess the impact of specific surface area on drug release. Then, two types of sustained-release gliclazide tablets were developed and evaluated in vitro. One involved side-coating the tablets with an ethylcellulose solution. The second was a novel three-layer donut-shaped tablet. Finally, these novel sustained-release tablets were evaluated for in vivo drug release and pharmacokinetics in rabbits. Results After lateral coating, commercial tablets altered drug release from first-order to zero-order kinetics. Tablets with the same specific surface area, but different diameters and thicknesses, can have similar release profiles. If the drug release area is unchanged, the tablet typically exhibits zero-order release behavior. Thus, we developed two types of gliclazide sustained-release tablets with a constant release area that achieved zero-order drug release. In vivo, they showed smoother plasma concentration profiles with lower C max , extended T max , and reduced fluctuation, and were bioequivalent to commercial tablets in pharmacokinetic studies. Conclusions Stable drug release can be achieved by maintaining a constant release area. In this study, the novel tablet preparations exhibited consistent drug release both in vivo and in vitro.