Model-Based Scale-up Methodologies for Pharmaceutical Granulation
Eun Ha Jang, Yun Sang Park, Min‐Soo Kim, Du Hyung Choi
Abstract
In the pharmaceutical industry, it is a major challenge to maintain consistent quality of drug products when the batch scale of a process is changed from a laboratory scale to a pilot or commercial scale. Generally, a pharmaceutical manufacturing process involves various unit operations, such as blending, granulation, milling, tableting and coating and the process parameters of a unit operation have significant effects on the quality of the drug product. Depending on the change in batch scale, various process parameters should be strategically controlled to ensure consistent quality attributes of a drug product. In particular, the granulation may be significantly influenced by scale variation as a result of changes in various process parameters and equipment geometry. In this study, model-based scale-up methodologies for pharmaceutical granulation are presented, along with data from various related reports. The first is an engineering-based modeling method that uses dimensionless numbers based on process similarity. The second is a process analytical technology-based modeling method that maintains the desired quality attributes through flexible adjustment of process parameters by monitoring the quality attributes of process products in real time. The third is a physics-based modeling method that involves a process simulation that understands and predicts drug quality through calculation of the behavior of the process using physics related to the process. The applications of these three scale-up methods are summarized according to granulation mechanisms, such as wet granulation and dry granulation. This review shows that these model-based scale-up methodologies provide a systematic process strategy that can ensure the quality of drug products in the pharmaceutical industry.