(M0930-08-55) Worsened Punch Sticking by External Lubrication with Magnesium Stearate

Purpose: Punch sticking, an outstanding problem in tablet manufacturing, is defined as the adherence of the powder material onto the tooling surface during powder compaction. ^{1 2} Externally lubricating tablet tooling with magnesium stearate (MgSt) before compression is commonly used to prevent punch sticking. ³ However, we surprisingly observed that external lubrication actually worsened punch sticking problems when compressing several materials. Hence, this work was carried out to gain a mechanistic understanding of this counterintuitive phenomenon.

Methods: We quantified punch-sticking propensity by measuring weight change after each compression using an upper punch with a removable tip coated with a layer of MgSt. Punch sticking leads to an increase in weight, whereas an absence of punch sticking leads to a negative weight change as MgSt is transferred from the punch tip to tablet. Weight gains as a function of compaction pressure, ranging 4 - 200 MPa, was used to profile punch sticking property of each powder. The in-die tablet porosity vs. pressure data was collected using a compaction simulator (Styl’One), which was analyzed using the Heckel equation to obtain the parameter, mean yield pressure (P_y), to quanitify material plasticity. ⁴

Results: Qualitatively similar punch sticking profiles were observed for all four compounds. With increasing pressure, weight initially increased and then decreased to eventually reach a net loss (Figure 1). We hypothesized that, whether or not API particles are transferred to punch tip depends on relative strengths of three forces pertaining to powder compaction, i.e., 1) MgSt and API (F_ma); 2) MgSt and punch (F_mp); and 3) API and API (F_aa). When MgSt is more plastic than API, the highly plastic MgSt layer can deform readily to develop a larger bonding area with the API particles in contact than that between API particles. Hence, F_ma rises more sharply than F_aa to reach a plateau (Figure 2). On the other hand, F_mp is independent of pressure as the bonding area between MgSt and punch has already reached a maximum before compression (Figure 2). Therefore, the condition of F_mp > F_ma > F_aa is satisfied in a low pressure range (Figure 2), under which API particles will be transferred to the MgSt layer, leading to punch sticking. The weight would increase with increasing pressure till F_ma = F_aa, which corresponds to a maximal weight gain. As F_aa surpasses F_ma with further increase in pressure, the peeling off of MgSt from punch tip results in a negative weight change. The observation that all four model powders are less plastic than MgSt, based on their in-die P_y values (Table 1), provides strong support to the hypothesized punch sticking mechanism.

Conclusion: The counterintuitive observation of worsened punch-sticking phenomenon of API when punches were lubricated with MgSt was explained using a model that considers the interplay among F_mp , F_ma , and F_aa as a function of both pressure and mechanical properties of API and MgSt. This model was qualitatively supported by all four powders investigated.

References: (1) Chattoraj, S.; Daugherity, P.; McDermott, T.; Olsofsky, A.; Roth, W. J.; Tobyn, M. Sticking and Picking in Pharmaceutical Tablet Compression: An IQ Consortium Review. J. Pharm. Sci. 2018, 107 (9), 2267–2282. https://doi.org/10.1016/j.xphs.2018.04.029.
(2) Paul, S.; Taylor, L. J.; Murphy, B.; Krzyzaniak, J.; Dawson, N.; Mullarney, M. P.; Meenan, P.; Sun, C. C. Mechanism and Kinetics of Punch Sticking of Pharmaceuticals. J. Pharm. Sci. 2017, 106 (1), 151–158. https://doi.org/10.1016/j.xphs.2016.07.015.
(3) Gunawardana, C. A.; Kong, A.; Blackwood, D. O.; Travis Powell, C.; Krzyzaniak, J. F.; Thomas, M. C.; Calvin Sun, C. Magnesium Stearate Surface Coverage on Tablets and Drug Crystals: Insights from SEM-EDS Elemental Mapping. Int. J. Pharm. 2023, 630, 122422. https://doi.org/10.1016/j.ijpharm.2022.122422.
(4) Vreeman, G.; Sun, C. C. Mean Yield Pressure from the In-Die Heckel Analysis Is a Reliable Plasticity Parameter. Int. J. Pharm. X 2021, 3, 100094. https://doi.org/10.1016/j.ijpx.2021.100094.

Table 1. In-die Py values of APIs and MgSt.

Figure 1. The weight gain plots versus compaction pressure of punch tip after compression for a) sodium cyclamate; b) celecoxib; c) ibuprofen; d) acetaminophen.

Figure 2. An illustration of the mechanism underlying the MgSt induced punch sticking phenomenon, considering the interplay among Faa, Fma, and Fpm, as a function of compaction pressure.