Early prediction of tablet defects during pan coating

The appearance of a tablet is a critical quality attribute that can be directly evaluated by patients. During tablet manufacturing, mechanical stress may lead to visual defects, such as edge chipping, the prediction of which remains a major challenge, particularly during technology transfer or scale-up processes. This study aimed to evaluate whether the number and severity of defects could be predicted under two mechanical stress environments: pan coating and friabilator testing.

A breakage model was calibrated using drop tests with two placebo formulations: mannitol:microcrystalline cellulose (7:3) and microcrystalline cellulose:anhydrous dibasic calcium phosphate (7:3), both at target tensile strengths of 1.5–2.5 MPa. Discrete element method (DEM) simulations were used to estimate the collision velocities and frequencies in the coating pan, enabling defect prediction using the breakage model. One verification run was performed using the mannitol:MCC 7:3 formulation at 2.0 MPa, which was also used to predict the tablet appearance in the friabilator.

The model accurately predicted the severity of defects (Classes I–III, where I is the least and III the most severe defect) in the coating trial but underestimated the number of Class I defects. The numerical predictions made by the model are exponentially affected by inaccuracies in the calibration of model parameters, particularly for small damage. Visual differences between tablets with equal mass loss in the friabilator and pan coater also suggest that wear from low-force collisions contributed to damage during the coating process. In contrast, the number of appearance defects was overpredicted in the friabilator, highlighting the model’s limitations in systems with frequent collisions. Overall, with careful calibration and under conditions with few defect-causing events, the model can provide useful guidance for defect prediction.

Highlights

A breakage model calibrated by tablet drop tests was used to predict defect
The severity of defects to tablet appearance was predicted accurately
The number of expected defects was underpredicted in a pan coating trial
The number of defects which occur in a friabilator was overpredicted.

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Materials

Two placebo formulations were used in this study. The first formulation consisted of mannitol (MAN) (Pearlitol 100 SD, Roquette, Lestrem, France) and microcrystalline cellulose (MCC) (Avicel PH-102, FMC International Health and Nutrition, Cork, Ireland) in a 7:3 mass ratio. The second formulation consisted of microcrystalline cellulose and anhydrous calcium hydrogen phosphate (DCPA) (Emcompress Anhydrous, JRS Pharma, Rosenberg, Germany) in a 7:3 mass ratio. The 7:3 ratio between the two components was used to obtain a balanced plastic-brittle behavior (Roberts and Rowe, 1987), in contrast to behavior observed in single-component systems. In addition, 1.5% w/w magnesium stearate (Peter Greven, Venlo, Netherlands) was used as a lubricant in both formulations.

Joona Sorjonen, Luis Martin de Juan, Pirjo Tajarobi, Håkan Wikström, Jarkko Ketolainen,
Early prediction of tablet defects during pan coating,
European Journal of Pharmaceutical Sciences, 2025, 107414, ISSN 0928-0987,
https://doi.org/10.1016/j.ejps.2025.107414.