Assessing Tablet-Sticking Propensity

The authors designed an upper punch with a removable punch tip to determine a tablet formulation's propensity to stick by weighing the mass of powder adhered to the punch tip.
Jan 02, 2012
Volume 36, Issue 1

The adherence or sticking of compressed powder to the surfaces of tablet tooling can cause significant drug-product manufacturing problems and quality defects, such as surface picking, surface dulling, and illegible tablet debossing. The literature contains several methods for assessing the degree of punch sticking, including chemical analysis of dissolved material adhered to the punch tip, visual inspection of punch tips, measurement of tablet take-off forces, powder-impingement testing, and measurement of punch pull-off force using an instrumented punch (1–6). Although these methods are useful, simple and quantitative punch-sticking-assessment tools are lacking, and many tablet-formulation scientists have continued to assess the severity of sticking by visually inspecting the tooling surface or the tablet. A reliance on visual inspection represents a significant gap in a formulator's toolbox because the technique is based on subjective opinion, and it is nearly impossible to systematically benchmark sticking behavior with different active ingredients, formulation components, operators, processing conditions, and manufacturing dates.

Figure 1: Theoretical calculation of the mass of powder adhered to a punch tip as a function of powder-layer thickness, assuming a 0.5-in., round, flat-faced punch is used and the true density of the adhered layer is 1.5 g/cc.
The authors aimed to design and test a custom tableting punch with a removable tip that would allow users to quantitatively assess material sticking to tooling surfaces by weighing the adhered powder. This approach for measuring the adhered powder has not been put into practice because of the practical difficulties inherent in accurately measuring an extremely small quantity of adhered powder (i.e., micrograms) on a punch that weighs ~100 g. Therefore, a removable punch tip with a low mass (i.e., < 5 g) that can be weighed on a microbalance solves this problem. A simple calculation of the weight of powder adhered to a 12.7-mm diameter flat-faced punch tip suggests that a uniform film thickness as thin as 0.1 µm can be detected using a microbalance, assuming a sample true density of 1.5 g/cc (see Figure 1). This limit of detection is reasonable because the particle diameters of most pharmaceutical powders are greater than 1 µm. In this study, a custom-designed punch with a removable tip was assessed as a method for quantitatively evaluating punch-sticking behavior of formulations containing various concentrations of sticky powders in tablet formulations.


Ibuprofen (50 grade, BASF) and mannitol (spray dried, granular, and powder grades, SPI Pharma) were chosen as sticky powders and mixed in glass bottles using a Turbula blender (Quadro Engineering) for 5 min with microcrystalline cellulose (Avicel PH102, FMC Biopolymer) as a common, nonsticky tableting diluent and magnesium stearate (HyQual, Mallinckrodt Baker) as a tableting lubricant. In addition, a prototype formulation containing 50% w/w ibuprofen, 5% w/w talc (IMI Fabi), and other proprietary components was tested alongside commercial ibuprofen blends, including Advil tableting blend (Pfizer), Albermarle ibuprofen 85 (Albe-tab DC85), and BASF ibuprofen (DC85 grade).


Figure 2: Custom F-type punch with removable tip for tablet punch-sticking assessments, including (left) setscrew, (middle) removable tip, and (right) fully assembled punch.
A custom F-type upper punch with a removable tip was designed to be fitted on a single-station laboratory eccentric tablet press (Manesty F3, see Figure 2). The 0.5-in. diameter, round, flat-faced tip was attached to the punch barrel using two set screws in series that seated against the stem of the removable tip. The tip had a mass of approximately 3 g so that it and any accumulated powder could be weighed periodically using a high-precision balance after compressing tablets. The custom upper punch, a standard lower punch, and standard die were installed on the tablet press. The press was operated under power at a rate of 3000 compressions/h to produce 2–3-mm thick tablets with weights of 250 mg and diameter of 12.7 mm at a solid fraction of 0.85. The punch tip was removed, weighed using a microbalance (MT5, Mettler-Toledo), and reinstalled periodically during the compression run.

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