Comparing environmental impacts of direct compaction versus wet granulation tableting methods for drugs with poor flowability by life cycle assessment

Pharmaceutical tablet productions by direct compaction (DC) are more environmentally sustainable than wet granulation (WG) owed to DC’s lower energy consumption. For drug particles with poor flowability, however, the environmental benefits of DC become questionable because DC of such drugs requires either pre-compaction treatment, increased excipients’ proportion in the tablets, or using excipients with unfavorable sustainability profiles. Using ibuprofen (IBU) as the model drug with poor flowability, we performed cradle-to-gate life cycle assessment (LCA) using ReCiPe 2016 method to characterize the environmental impacts of DC and WG tablet productions. Material and energy flow data from laboratory-scale (1 and 2.2 kg IBU) and simulated pilot-scale (25 kg IBU) productions were utilized in the LCA. Despite the increased proportion of excipients with less-than-ideal sustainability profile in DC tablets, the environmental impacts of DC tablet production remained smaller than WG tablet production across different production scales, as the impacts were governed by process-level energy consumption. The impacts of DC and WG tablet productions, nevertheless, became closer in magnitude with increasing production scale attributed to superior improvements in the energy requirement and yield of WG tablets. Thus, the environmental beneftis of DC tablets over WG tablets was diminished for drugs with poor flowability.