Metta, Nirupaplava. Model development and analysis of solid oral dosage manufacturing processes involving particle size change. Retrieved from https://doi.org/doi:10.7282/t3-7n9q-a703
DescriptionContinuous pharmaceutical manufacturing offers advantages in cost, efficiency and acceleration in process development, particularly in the time of increasing research and development, and production costs. A science-based approach to process development promoted by the Quality by design paradigm requires incorporating the effect of variability in material properties and process conditions on product properties. This has increased focus on development of detailed and complex models capturing phenomenon from several scales, which led to an increase in computational expense. The limitations are exacerbated when several such models are integrated to simulate a continuous manufacturing process. This dissertation explores several modeling methods for the development of hybrid models of particulate processes. Milling operation is used as a case study for hybrid model development that supports the Quality by design approach and also addresses computational limitations. Several unit operation models are integrated to simulate a wet granulation continuous manufacturing process leading to a computationally expensive model with several variables. This dissertation also establishes efficient methodologies to utilize the high dimensional and computationally expensive integrated process models for obtaining the space in which process needs to operate, thus supporting continuous pharmaceutical process development.