Robustness

In recent years, there is a continuous drive from pharmaceutical companies and regulatory bodies to develop more robust pharmaceutical formulations and processes based upon knowledge. This has resulted in a request to excipient suppliers to help de-risking the use of their excipients, in line with quality-by-design. Consistency of excipients is key to ensure consistent performance of every produced final dosage form. 

Principle Component Analysis (PCA) is a multivariate technique used by DFE Pharma to investigate patterns and clusters in large product data sets. Each dot in a score plot represents a batch and each color a year of production. A high degree of overlap of datapoints shows that there is a high batch-to-batch and year-to-year consistency.

Robustness of a formulation can be ensured by using excipients with proven consistency.

  • Understanding excipient variability can de-risk the use of excipients by ensuring the use of the same physical and chemical properties during development and production
  • Ensured year-after-year, batch-after-batch consistency provides confidence in product consistency over the entire marketed period of a drug product

Robustness of a formulation can be obtained by the use of excipients with low process sensitivity.

  • Switch to less elastic excipients to reduce dwell time and lubricant sensitivity (e.g. switch from MCC to lactose)
  • Increase surface area of excipients to reduce lubricant sensitivity
  • Select excipients with optimal morphology to reduce lubricant sensitivity; flat surfaces delaminate lubricant more easily and are therefore more sensitive to over lubrication
  • Granulated lactose grades provide the lowest lubricant sensitivity
  • SuperTab® 40LL provides the lowest dwell time sensitivity
  • Plastic excipients, like MCC, often result in low ejection forces which can increase the tooling lifespan