Abina M. Crean
SSPC, the SFI Research Centre for Pharmaceutical Research, School of Pharmacy, University College Cork, Ireland
Efficient pharmaceutical tablet production processes necessitate careful consideration of formulation design. Robust tablet blends rely on good blend flow and compaction properties. However, active pharmaceutical ingredients (API) can present challenges to tablet blend flow and compactability, compromising overall tableting performance.
The presentation will highlight the impact of suboptimal tablet formulation on tablet quality and throughput at a commercial scale through experimental examples. The shortcomings of suboptimal API properties on blend performance can be addressed by formulation and process design strategies, informed by an understanding of the relationships between blend, tablet process, and subsequent tablet properties. Experimental approaches and theoretical frameworks that guide robust tablet blend design and predict blend tabletability will be presented. Examples will include the utilization of powder flow parameters and the compaction triangle (Tye et al., 2005) to assess both API and blend flow and compaction behaviour. The Manufacturing Classification System (MCS) framework, which considers the impact of API physical properties on tablet manufacturability and aims to inform tablet production route (direct compression or tableting via granulation) based on API properties, will be discussed (Leane et al., 2015). Additionally, the relevance of the MCS for continuous tablet production will be explored. The concept of a critical API blend fraction, above which an abrupt shift in blend behaviour can occur, will be presented, along with the application of percolation threshold theory to determine this threshold. Finally, opportunities and challenges associated with the compaction of peptide/protein API will be presented with illustrative examples from ongoing compaction studies.
References
Leane, M., Pitt, K., & Reynolds, G. (2015). A proposal for a drug product Manufacturing Classification System (MCS) for oral solid dosage forms. Pharmaceutical Development and Technology, 20(1), 12–21. https://doi.org/10.3109/10837450.2014.954728
Tye, C. K., Sun, C. (Calvin), & Amidon, G. E. (2005). Evaluation of the effects of tableting speed on the relationships between compaction pressure, tablet tensile strength, and tablet solid fraction. Journal of Pharmaceutical Sciences, 94(3), 465–472. https://doi.org/https://doi.org/10.1002/jps.20262