Influence of solid form impurity on punch sticking propensity of carbamazepine.

Punch sticking is a well-recognized and extensively studied challenge in pharmaceutical tablet manufacturing. However, the impact of solid-form impurities in formulations on sticking propensity has not been adequately investigated. Here, we examined the effect of solid-form impurities on the punch sticking behavior of two carbamazepine batches (CBZ-A and CBZ-B), obtained from different suppliers. CBZ-B contained a mixture of form III and CBZ dihydrate (CBZd), whereas CBZ-A consisted exclusively of form III. CBZ-B exhibited a substantially greater tendency to stick than CBZ-A. To further elucidate the factors influencing sticking, a design of experiments (DOE) approach was employed using CBZd to investigate the effect of particle size, compaction pressure, and active pharmaceutical ingredient (API) loading on sticking mass. The results show that sticking was exacerbated by smaller particle size, lower compaction pressure, and higher API loading. In addition, a significant interaction between particle size and API loading was identified, indicating that these variables jointly influence sticking propensity. These findings highlight the importance of controlling not only the solid-state phase purity of the API but also particle size, API loading, and compaction pressure to ensure robust tablet manufacturing.