Simple Quantification of Sticking Propensities of Pharmaceuticals with Mechanochemistry.

Punch sticking poses significant challenges in tablet manufacturing and the need for effective solutions is ever-growing. Direct sticking assessment methods often rely on bulky, material-consuming equipment such as compactor emulators, only available in manufacturing sites, and thus inaccessible for most research labs. Consequently, there only exists limited data on sticking propensities of pharmaceuticals in the literature, significantly limiting our understanding of the issue and how it impacts drug manufacturing. A novel, easy, material-sparing, and lab-friendly method to evaluate sticking trends across diverse systems is presented here. The method employs a mechanochemical technique (ball mill grinding) to measure the materials' adherence to a stainless-steel substrate (milling ball). After optimization of the operating parameters such as relative humidity pretreatment of materials, a best practice protocol was developed. We measured the sticking propensities of 19 diverse molecular crystalline systems consisting of active pharmaceutical ingredients (APIs), API precursors, and common excipients. The method was effective at differentiating and quantifying the sticking ability of our diverse set of systems, which were classified into low sticking (<30 g/m