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Development of materials by mixing different base components is a widespread methodology to create materials with improved properties compared to those of its base components. However, efficient determination of the properties of mixture-based materials during design remains challenging without prior knowledge of the underlying physical phenomena. In this work a new data-based methodology is proposed involving the use of probabilistic, knowledge-guided artificial neural networks to jointly model the properties of the base components, the proportions in which they are mixed, and the processing conditions used during manufacture to predict properties of final products. The method proposed does not involve any assumptions in terms of ideal mixing rules of the base components, and allows for estimation of aleatoric uncertainty in the prediction. Additionally, an extension is presented that incorporates expert knowledge into the model by the implementation of monotonicity constraints between certain inputs and outputs. The methodology is illustrated with a case study involving the formulation of drug products using direct compression. The model is used to predict pharmaceutical tablets' quality attributes (mass variation, tensile strength, disintegration time, friability and ejection force), showing that the method is able to predict properties of the final product overcoming gaps currently present in previous modelling approaches., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Cosmetic inspection of freeze-dried products is an important part of the post-manufacturing quality control process. Traditionally done by human visual inspection, this method poses typical challenges and shortcomings that can be addressed with innovative techniques. While many cosmetic defects can occur, some are considered more critical than others as they can be harmful to the patient or affect the drug's efficacy. With the rise of artificial intelligence and computer vision technology, faster and more reproducible quality control is possible, allowing real-time monitoring on a continuous manufacturing line. In this study, several continuously freeze-dried samples were prepared using formulations and process settings that lead deliberately to specific defects faced in freeze-drying as well as defect-free samples. Two approaches (i.e. patch-based approach and multi-label classification) capable of handling high-resolution images based on Convolutional Neural Networks were developed and compared to select the optimal one. Additional visualization techniques were used to enhance model understanding further. The best approach achieved perfect precision and recall on critical defects, with a prediction time of less than 50 ms to make a decision on the acceptance or rejection of vials generated., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier B.V. All rights reserved.)

The pharmaceutical industry is progressing towards more continuous manufacturing techniques. To dry biopharmaceuticals, continuous freeze drying has several advantages on manufacturing and process analytical control compared to batch freeze-drying, including better visual inspection potential. Visual inspection of every freeze-dried product is a key quality assessment after the lyophilization process to ensure that freeze-dried products are free from foreign particles and defects. This quality assessment is labor-intensive for operators who need to assess thousands of samples for an extensive amount of time leading to certain drawbacks. Applying Artificial Intelligence, specifically computer vision, on high-resolution images from every freeze-dried product can quantitatively and qualitatively outperform human visual inspection. For this study, continuously freeze-dried samples were prepared based on a real-world pharmaceutical product using manually induced particles of different sizes and subsequently imaged using a tailor-made setup to develop an image dataset (with particle sizes from 50μm to 1 mm) used to train multiple object detection models. You Only Look Once version 7 (YOLOv7) outperforms human inspection by a large margin, obtaining particle detection precision of up to 88.9% while controlling the recall at 81.2%, thus detecting most of the object present in the images, with an inference time of less than 1 s per vial., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)