Investigating the effect of MCC content in the formulation on product attributes in continuous powder to tablet manufacturing line

Continuous manufacturing (CM) offers improved efficiency and control in pharmaceutical production, but the influence of formulation on the stability performance across the unit operations remains a critical challenge. This study aims to establish a link between process outcomes with final product quality by investigating the effect of microcrystalline cellulose (MCC) content on the process performance and tablet properties in a continuous powder to tablet line (Consigma-25). Powder blends containing three ratios of lactose and MCC were processed under fixed operating conditions through twin-screw wet granulation, fluidized bed drying, conical milling, lubricant blending, and tableting. Inline Process Analytical Technologies (PAT), including built soft sensor, a near-infrared (NIR) moisture probe and a real-time granule size measurement probe, were employed to monitor in-process material behaviour. Produced tablets were collected over time and examine the properties. X-ray imaging technique was employed to evaluate tablet internal structure. Under fixed process settings, powder blend with reduced MCC content shows increased powder caking within the granulator, lower moisture content after drying, and higher bulk density of the milled granules. This led to higher tablet weight and higher actual tablet compression force, contributing to the formation of internal cracks in the tablet cross section area. In contrast, tablets with a higher MCC content showed more pronounced flashing problem, even though at relatively low actual compression force, the tablets showed extended edges during compression. In general, tablet tensile strength increases with higher MCC content; however, the actual compression force remains a critical factor influencing the extent of strength development. These observations emphasize the importance to consider both formulation and process settings when targeting optimal tablet performance in continuous manufacturing.