Bartłomiej Pesta, Marzena Jamrógiewicz, Małgorzata Sznitowska

Characterization of granulation process and product with the usage of advanced physical methods

2025-10-31

Wet granulation is the most commonly used indirect process in the production of solid oral dosage forms when direct compression is not possible. This method of granulation is particularly important due to availability of equipment and the relatively easy implementation of numerous process variables, which allows control of the properties of the granulate. Although this technique is not new, in light of the current “Quality by Design, QbD” approach, in-depth knowledge and understanding of the process becomes a challenge. The usage of advanced physical analysis techniques, including online process control tools for assessing the properties of the final product can be helpful in achieving these goals.

To optimize the wet granulation process, numerous physical and thermodynamic associations are used to characterize and understand the physical phenomena that occur during the agglomeration of powder particles using wetting liquid binders. This article defines and explains the importance of the Weber number, capillary forces, wettability index, and granulate bulk density. Various liquid binders are also presented, along with examples of the physicochemical interactions and their applications in pharmaceutical technology. A summary of variable parameters that characterizes high-shear granulation is prepared and their impact on granulate quality is discussed. A list of the process variable parameters was prepared and their impact on the quality of granules was discussed. The original element of the study is a review of modern analytical methods in the context of their current application in assessing the physical properties of granules, not only in the obtained product, but also during the process. Analytical tools and process analysis technologies used for the characteristics of the granulation process were reviewed, with a special emphasis to their practical use in high-shear wet granulation.

This review provides a comprehensive characterization of granulates and the high-shear granulation process, with particular attention paid to the impact of process parameters on the quality of the obtained granulate. The novelty element of the study is the interdisciplinary connection of technological parameters with physicochemical particle binding mechanisms, which allows for a fuller understanding of the process. Advanced physical analysis techniques have been presented, which can be used to analyze the granulation process under the so-called Process Analytical Technology (PAT), for better knowledge and process control in accordance with the assumptions of the QBD concept, and the novelty of this study is their critical combination with the prospect of implementation.

Keywords: high-shear wet granulation, Quality by Design, Process Analytical Technology (PAT).

© Farm Pol, 2025, 81(2): 81–94