(442a) The effect of Magnesium Stearate and Colloidal Silicon Dioxide interaction on binary mixture flowability and picking tendency of market image tablets

Direct compression of drug product formulations with embossed tooling can result in picking of the resultant tablet face. Magnesium stearate (MgSt) is a widely used lubricant in tablet formulations to reduce particle-surface adhesion during compression. Colloidal silicon dioxide (CSD) is another excipient used in small amounts (< 1.5 wt%) within drug product formulations to improve powder flowability by coating larger particles. Previously it has been identified that the surface coverage provided by CSD can negatively impact the lubrication efficacy of MgSt (Sabir 2001), thus increasing the opportunity for picking events to occur. Understanding the MgSt and CSD interaction is critical as tablet picking problems typically occur in later stages of production when a process is scaled up. Therefore, identifying the potential for picking in early development can prevent future yield losses and help quantify minimum and maximum concentrations of MgSt and CSD, respectively. The nature of this interaction and its resultant effect on the mixture blend properties and tablet is investigated as a function of the relative amounts of these two excipients in binary mixtures of lactose monohydrate and microcrystalline cellulose using a single embossed compression tooling. The interaction of CSD and MgSt within the formulation is observed under scanning electron microscopy (SEM) and the surface coverage quantified via SEM-based energy dispersive X-ray spectroscopy (SEM-EDS). The formulation’s resistance to flow is measured by ring shear testing (RST.Xs) and dynamic flow testing (FT4). The formulation is then compressed on a compaction simulator and its impact on the take-off force, ejection force, evidence of picking via visual inspection, and tablet tensile strength is analyzed.

Reference: Sabir, A., Evans, B., Jain, S., 2001. Formulation and process optimization to eliminate picking from market image tablets. Int. J. Pharm. 215 (1-2), 123–135.