Understanding the role of magnesium stearate in lowering punch sticking propensity of drugs during compression

The sticking of active pharmaceutical ingredient (API) to the surfaces of compaction tooling, frequently referred to as punch sticking, causes costly downtime or product failures in commercial tablet manufacturing. Magnesium stearate (MgSt) is a common tablet lubricant known to ameliorate the sticking problem, even though there exist exceptions. The mechanism by which MgSt lowers punch sticking propensity (PSP) by covering API surface is sensible but not yet experimentally proven. This work was aimed at elucidating the link between PSP and surface area coverage (SAC) of tablets by MgSt, in relation to some key formulation properties and process parameters, namely MgSt concentration, API loading, API particle size, and mixing conditions. The study was conducted using two model APIs with known high PSPs, tafamidis (TAF) and ertugliflozin-pyroglutamic acid (ERT). Results showed that PSP decreases exponentially with increasing SAC by MgSt. The composition of material stuck to punch face was also explored to better understand the onset of punch sticking and the impact of possible MgSt-effected punch conditioning event.

Materials

The two model drugs, TAF and ERT, were provided by Pfizer, which included three batches of ERT with different mean particle sizes, labeled in the text as large (L), medium (M) and small (S). The true densities of TAF and ERT, determined by a helium pycnometer (AccuPyc II, Micromeritics Instrument Corp., Norcross, Georgia, USA), are 1.57 and 1.41 g·cm^-3, respectively. Microcrystalline cellulose (MCC; Avicel PH-102, DuPont), dicalcium phosphate anhydrate (DCPA; A-Tab, Innophos), crospovidone (CP;

Chamara A. Gunawardana, Angela Kong, Debbie Wanapun, Daniel O. Blackwood, C. Travis Powell, Joseph F. Krzyzaniak, Myles C. Thomas, John E. Kresevic, Changquan Calvin Sun, Understanding the role of magnesium stearate in lowering punch sticking propensity of drugs during compression, International Journal of Pharmaceutics, 2023, 123016, ISSN 0378-5173,
https://doi.org/10.1016/j.ijpharm.2023.123016.

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