Reducing the experimental effort to design pharmaceutical tablet lubrication by model-based design of experiments

In oral solid-dosage manufacturing through direct compression, lubrication is used to enhance powder flowability and the ejection of the tablet from the die. However, lubrication can negatively impact tablet quality attributes such as tablets hardness or dissolution. In order to facilitate the selection of an appropriate lubrication extent, different models describing the relation between compaction performance and process conditions may be used. In particular, the extension of the Kushner and Moore model proposed by Nassar et al. (Nassar et al., 2021, Int. J. Pharm., 592, 119980) allows predicting tensile strength over a wide range of tablets solid fraction and powder blending time values. The main drawback of this model is that it requires a large number of experiments for parameter estimation. This results into a significant consumption of active pharmaceutical ingredient (API), which may be scarce and considerably expensive. In this study, model-based design of experiments is used to reduce the required experimental effort for the identification of the model parameters. We propose a novel procedure that is able to reduce parameters uncertainty while minimizing the number of required experiments. Results based on a simulated case-study demonstrate the effectiveness of the approach.