Continuous Granulation-Based Tableting

To examine the sustainability of batch versus continuous granulation-based tablet manufacturing from a resource point of view, an Exergy Analysis — on both process and plant level — and an ELCA at three different levels was done to identify and locate resource losses throughout the pharmaceutical production chain. Three major boundary systems were defined. The alpha level (process level) represents tablet manufacturing (granulation, coating, tablet compression, etc.). The beta level (plant level) represents the on-site supporting core processes (steam generation, for example). The overall industrial environmental processes in the technosphere define the gamma level.

Shifting from batch to continuous production by implementing a ConsiGma® system (continuous production line, based on twin screw granulation) resulted in an exergetic resource consumption reduction of 10.19% (65.6 to 58.9 kJex/tablet), 15.21% (111 to 94.0 kJex/tablet) and 2.38% (2.14 to 2.08 MJex/tablet) at process (a), plant (ß) and overall industrial level (g), respectively. Focusing on formulation by excluding API and packaging material constituent production (transit exergy) resulted in a reduction of 33.99% (19.1 to 12.6 kJex/tablet), 25.89% (64.6 to 47.7 kJex/tablet) and 14.69% (138 to 118 kJex/tablet) at the respective boundary systems.

The results obtain for highly potent drugs (high API weight percentage); and, for low dose drugs (API weight reduction of 50%), sensitivity analysis showed a resource consumption reduction of 38% within the cradle-to-gate approach (gamma). This is, at a lifecycle level, the most relevant way of expressing savings in drug product production processes (independent of the API production step), to ensure that the contribution made to resource reduction by continuous production is not underestimated.

To conclude, the potential implementation of a continuous ConsiGma® production line at a pharmaceutical manufacturing plant (Janssen-Cilag SpA, in this example) would be a significant step forward towards “green engineering” and more environmentally friendly pharmaceutical manufacturing. Recent developments towards in-line blending and coating would reduce the environmental burden of drug production processes even further.

Reference

W. De Soete, et al., “Exergetic Sustainability Assessment of Batch versus Continuous Wet Granulation Based Pharmaceutical Tablet Manufacturing: A Cohesive Analysis at Three Different Levels,” Green Chem. 15, 3039–3048 (2013).