Junshu Zhao, Jasen Zhang, Brian Zacour, Sherif Badawy
Bristol-Myers Squibb, 1 Squibb Dr, New Brunswick, NJ

Purpose. SDD materials have unique compaction properties such as strong force sensitivity and high elastic recovery compared to crystalline APIs as a result of their high polymer content and the hollow structure. These properties can increase the compaction risk and result in higher tablet hardness variabilities and defects, especially when SDD is present in high loadings in the overall formulation. The presentation will overview the compaction risk of high SDD formulations and provide formulation recommendations to reduce the risk based on the studies conducted.

Methods. The Drucker-Prager Cap (DPC) model was used to assess the compaction risk of high SDD loading formulations (50-70%) from data generated by Stylcam compaction simulator. The risk was verified by a material-sparing approach that simulates the roller compaction and compression process using Stylcam.

Results. DPC analysis suggested reduced compaction risk with increasing brittle excipients such as lactose and decreasing ductile excipients such as Microcrystalline Cellulose (MCC) for high SDD loading formulations. This was verified using the simulated roller-compaction and compression process at 70% SDD loading where tablet defect was observed for formulations that contains MCC as diluents while no defects were observed when lactose was used as the solo diluent.

Conclusions. DPC model is a useful tool for assessing the compaction risk of high SDD loading formulations. Stylcam compaction simulator also provides a material – sparing approach for simulating the roller compaction and compression process that can be used to verify the compaction risk. For formulations that requires high SDD loading, it is recommended to use more brittle diluents such as lactose to reduce the compaction risk.