A Machine Learning Approach to Qualitatively Evaluate Different Granulation Phases by Acoustic Emissions.

Wet granulation is a frequent process in the pharmaceutical industry. As a starting point for numerous dosage forms, the quality of the granulation not only affects subsequent production steps but also impacts the quality of the final product. It is thus crucial and economical to monitor this operation thoroughly. Here, we report on identifying different phases of a granulation process using a machine learning approach. The phases reflect the water content which, in turn, influences the processability and quality of the granule mass. We used two kinds of microphones and an acceleration sensor to capture acoustic emissions and vibrations. We trained convolutional neural networks (CNNs) to classify the different phases using transformed sound recordings as the input. We achieved a classification accuracy of up to 90% using vibrational data and an accuracy of up to 97% using the audible microphone data. Our results indicate the suitability of using audible sound and machine learning to monitor pharmaceutical processes. Moreover, since recording acoustic emissions is contactless, it readily complies with legal regulations and presents Good Manufacturing Practices.

Compression Density as an Alternative to Identify an Optimal Moisture Content for High Shear Wet Granulation as an Initial Step for Spheronisation.

Pellet production is a multi-step manufacturing process comprising granulation, extrusion and spheronisation. The first step represents a critical control point, since the quality of the granule mass highly influences subsequent process steps and, consequently, the quality of final pellets. The most important parameter of wet granulation is the liquid requirement, which can often only be quantitatively evaluated after further process steps. To identify an alternative for optimal liquid requirements, experiments were conducted with a formulation based on lactose and microcrystalline cellulose. Granules were analyzed with a Powder Vertical Shear Rig. We identified the compression density (ρpress) as the said alternative, linking information from the powder material and the moisture content (R2 = 0.995). We used ρpress to successfully predict liquid requirements for unknown formulation compositions. By means of this prediction, pellets with high quality, regarding shape and size distribution, were produced by carrying out a multi-step manufacturing process. Furthermore, the applicability of ρpress as an alternative quality parameter to other placebo formulations and to formulations containing active pharmaceutical ingredients (APIs) was demonstrated.