A framework for transferring sinomenine hydrochloride sustained-release tablet from batch to continuous direct compression manufacturing.

OBJECTIVE

To establish and validate a framework for the transfer of a sinomenine hydrochloride sustained-release tablet from a legacy batch process to a pilot-scale continuous direct compression (CDC) manufacturing line, without reformulation.

SIGNIFICANCE: Transferring existing products to continuous manufacturing (CM) without reformulation is challenging. In this work, a significant contribution is made through the validation of a data-driven pathway aligned with QbD and ICH Q13 to de-risk this transition.

METHODS

A pilot-scale CDC line, operating at 1.9 kg/h, was utilized, comprising loss-in-weight feeders, a continuous blender, and a rotary tablet press. A process analytical technology (PAT)-enabled control strategy was implemented, featuring a robust partial least squares (PLS) model developed for real-time API quantification via in-line near-infrared (NIR) spectroscopy. Process dynamics were characterized using residence time distribution (RTD) analysis.

RESULTS

Robust stability and control were demonstrated by the CDC process during a 300-minute steady-state run. Through real-time monitoring, API content uniformity was confirmed to be consistently maintained within ±3%. Critically, tablets produced via CDC were proven to be equivalent to the reference batch product across all critical quality attributes, including physical properties and functionally identical 24-hour dissolution profiles.

CONCLUSION

In this study, a comprehensive framework for the batch-to-continuous transfer of a sustained-release tablet was successfully validated. Process robustness was ensured by the PAT-enabled control strategy. Theapproach is confirmed as a low-risk, guideline-compliant pathway for modernizing the manufacturing of existing pharmaceutical products.