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

Abstract

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.

Highlights

Compression-coated tablets offer a cost-effective alternative to osmotic pump systems.

Compression-coated tablets exhibited similar in vitro and in vivo release to Xeljanz® XR.

Release behavior is tunable via release materials, pH modifiers, and tablet hardness.

This study extends the application of compression coating to sustained-release tablets.

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® 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 microenvironment 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 high-bioavailability sustained-release formulations, with significant potential for large-scale technological implementation.

Materials

Tofacitinib was provided by Shanghai Jinghao Pharmaceutical Co., Ltd. Glyceryl behenate was supplied by Gattefossé. Anhydrous lactose was obtained from Agropur (USA). Lactose F100 was provided by Meggle Group (Germany). Microcrystalline cellulose (MCC PH102) was purchased from JRS Pharma GmbH & Co. KG. Magnesium stearate was supplied by Looking Pharmaceutical Co., Ltd. (Zhejiang, China). Citric acid was purchased from Tianjin Hengxing Chemical Factory.

Zhitao Cai, Bei Liu, Han Zeng, Yu Zhang, Tian Yin, Haibing He, Jingxin Gou, Yanjiao Wang, Xing Tang, Sustained-release tablets prepared by compression coating technology achieve similar drug release to osmotic pump tablets: Process parameters and in vitro-in vivo evaluation, Journal of Drug Delivery Science and Technology, Volume 111, 2025, 107178, ISSN 1773-2247, https://doi.org/10.1016/j.jddst.2025.107178.