Sustained-release tablets prepared by compression coating technology achieve similar drug release to osmotic pump tablets: Process parameters and in vitro-in vivo evaluation

Over the past decades, a variety of controlled-release technologies have been developed to maintain a constant drug release rate in vivo. Osmotic pumps offer precise control and are widely used in marketed formulations. However, the manufacturing of osmotic pump tablets often involves additional steps like semipermeable membrane coating and laser drilling, which may increase the process complexity relative to simpler approaches such as compression coating. This study employed compression coating (CC) technology to prepare tofacitinib citrate sustained-release tablets (TOF SRTs), providing an alternative to osmotic pump tablets. By optimizing formulation and process parameters, we determined the appropriate amounts of glyceryl behenate as the sustained-release material (15 % in the core and 30 % in the coating) and the citric acid as the pH modifier (3 % in both the core and coating). The tablet core hardness was set at 25-30 N, and the overall tablet hardness was maintained at 100-110 N. Under these conditions, TOF SRTs achieved in vitro and in vivo drug release profiles similar to the commercially available formulation Xeljanz (R) XR, manufactured using osmotic pump technology. In vitro dissolution tests showed a similarity factor (f2) of 80.66, and pharmacokinetic studies in Beagle dogs revealed a relative bioavailability of 89.9 %. The technological breakthrough lies in its universal applicability. The release modulation mechanism, achieved by adjusting the ratio of sustained-release materials and micro-environment modifiers, as well as optimizing tablet core hardness, can be extended to other BCS II/IV drugs like apixaban and ibrutinib. This approach provides a novel strategy for the industrial production of highbioavailability sustained-release formulations, with significant potential for large-scale technological implementation.