Reduced Punch Sticking Propensity of Acesulfame by Salt Formation: Role of Crystal Mechanical Property and Surface Chemistry.

Abstract

Powder adhesion or sticking onto punches is one of the outstanding issues in pharmaceutical tablet manufacturing. We show in this work that, at comparable particle sizes, the acesulfame potassium exhibited pronouncedly reduced propensity to punch sticking than acesulfame. Detailed analyses revealed strong correlation between sticking propensity and crystal mechanical properties and surface chemistry. The free acid was highly plastic with high cohesive strength, while the salt form was brittle. During compaction, surfaces of acesulfame in contact with the punch face are abundant in electronegative functional groups, while those of the salt consist of mainly hydrophobic groups. Thus, acesulfame underwent stronger interactions with the electron-deficient punch. Consequently, the strikingly different onset and severity of sticking propensity between the two solid forms of acesulfame could be clearly explained based on their different crystal mechanical properties and surface characteristics. By providing molecular insight into the outstanding problem of punch sticking in tablet manufacturing, this work expands the list of pharmaceutical applications of crystal engineering.