(231g) Mitigating Punch Sticking Propensity of Celecoxib By Cocrystallization – an Integrated Computational and Experimental Approach

Punch sticking is an outstanding common problem that hinders commercial tablet manufacturing. The occurrence of punch sticking is evident when powder mass adheres onto tooling surfaces during the course of tablet compression. It causes poor tablet quality, such as rough tablet surface and inconsistent drug content, and results in low manufacturing efficiency due to the required intermittent process stoppage for cleaning. The commercial CEL (Form III) is an API with known high punch sticking propensity. An L-proline cocrystal of celecoxib was identified based on a computational approach for predicting crystal mechanical properties to significantly reduce the punch sticking propensity of celecoxib. The reduced punch sticking propensity by this cocrystal was attributed to both reduced plasticity through deactivating slip planes and minimizing exposure of high electronegative functional groups to punch tip during compression. This material sparing and reliable approach of integrated computational and experimental investigation of punch sticking holds promise in solid form selection of drugs for identifying crystal forms suitable for developing tablet formulations.