R&D To Product: How To Reduce Costly Scale-Up Problems

Scaling a new drug formulation from development to manufacturing often presents challenges, including process scale-up and formulation performance at production levels. Problems such as capping/lamination and sticking/picking usually emerge when a formulation undergoes the compression required for market supply. To mitigate these issues, preliminary experiments, including compaction profiles and strain rate sensitivity, are recommended. Though these tests can be costly and time-consuming, they provide valuable insights into the powder's performance under compression. If issues emerge, manufacturers should consult with the company providing the compression tools for potential modifications. Solutions for material sticking to the punch cup or die bore include testing a coating for reduced powder adhesion, reducing the clearance between the punch tip and die wall, or modifying the embossing letters. Running a full-scale performance lot can also preemptively identify potential problems. The article also discusses the importance of adjusting pre-compression and proper fill cam setting during tablet production scale-up. Overlooking these steps can lead to excess powder accumulation and variability in fill weight and tablet hardness.